tbuckley/cabot-search huggingface dataset:
Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients
Authors: J.Y. Pierga, M. Robain, M. Jouve, B. Asselain, V. Diéras, P. Beuzeboc, T. Palangié, T. Dorval, J.-M. Extra, S. Scholl, P. Pouillart
Journal: Annals of Oncology (2001)

In cancer patients, correlation between response to chemotherapy and gain in survival remains debated. We addressed this question in a multivariate analysis evaluating response to chemotherapy as a factor influencing survival of patients with metastatic breast cancer.From 1977 to 1992, 1430 patients included in eight consecutive prospective trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, were available for assessment. Median follow-up was 155 months.Median survival from the date of randomisation was 24 months. Objective response rate was 63.6%. A complete response (CR) was achieved in 17% (249 patients). In a stepwise forward progression analysis objective response was the first independent prognostic factor for survival. Median survival time was 43 months for complete responders (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5 months for progressive disease (PD). The probability of survival at 5 and 10 years was 35% and 15% for CR's and decreased to 18% and 6% for PR's. The timing of best response (at 4 or 8 months) was not related to outcome.Response to an anthracycline-based chemotherapy is a major independent prognostic factor in metastatic breast cancer. The use of this factor to investigate new drugs seems to be pertinent. The good prognosis of complete responders justifies further evaluation of new treatment strategies for this patient population.
Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors
Authors: K. S. Panageas, A. S. Reiner, F. M. Iwamoto, T. F. Cloughesy, K. D. Aldape, A. L. Rivera, A. F. Eichler, D. N. Louis, N. A. Paleologos, B. J. Fisher, L. S. Ashby, J. G. Cairncross, G. B. Roldan Urgoiti, P. Y. Wen, K. L. Ligon, D. Schiff, H. I. Robins, B. G. Rocque, M. C. Chamberlain, W. P. Mason, S. A. Weaver, R. M. Green, F. G. Kamar, L. E. Abrey, L. M. DeAngelis, S. C. Jhanwar, M. K. Rosenblum, A. B. Lassman
Journal: Neuro-Oncology (2014)

Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision making or to combine them for prognostication. We compiled a retrospective database of 1013 patients with newly diagnosed anaplastic oligodendrogliomas or oligoastrocytomas and performed a recursive partitioning analysis to generate independent prognostic classes among 587 patients with informative 1p19q status. Variables included for survival classification were age (continuous), history of prior low-grade glioma, 1p19q deletion status, histology (presence or absence of an astrocytic component), tumor lobe, tumor hemisphere, gender, extent of resection, postresection treatment, and performance status at diagnosis. Recursive partitioning analysis identified 5 prognostic groups based on hazard similarity: class I (age <60 y, 1p19q codeleted), class II (age <43 y, not codeleted), class III (age 43–59 y, not codeleted, frontal lobe tumor or age ≥60 y, codeleted), class IV (age 43–59 y, not codeleted, not frontal lobe tumor or age 60–69 y, not codeleted), and class V (age ≥70 y, not codeleted). Survival differences were highly significant (P < .0001), with medians ranging from 9.3 years (95% CI: 8.4–16.0) for class I to 0.6 years (95% CI: 0.5–0.9) for class V. These 5 distinct classification groups were defined using prognostic factors typically obtained during routine management of patients with anaplastic oligodendroglial tumors. Validation in a prospective clinical trial may better differentiate patients with respect to treatment outcome.
INTERNATIONAL OUTBREAK OF SALMONELLA EASTBOURNE INFECTION TRACED TO CONTAMINATED CHOCOLATE
Authors: PhilipC. Craven, WilliamB. Baine, DonaldC. Mackel, WilliamH. Barker, EugeneJ. Gangarosa, Martin Goldfield, Howard Rosenfeld, Ronald Altman, Gerard Lachapelle, JohnW. Davies, RichardC. Swanson
Journal: The Lancet (1975)
Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder
Authors: Stella J. de Wit, Pino Alonso, Lizanne Schweren, David Mataix-Cols, Christine Lochner, José M. Menchón, Dan J. Stein, Jean-Paul Fouche, Carles Soriano-Mas, Joao R. Sato, Marcelo Q. Hoexter, Damiaan Denys, Takashi Nakamae, Seiji Nishida, Jun Soo Kwon, Joon Hwan Jang, Geraldo F. Busatto, Narcís Cardoner, Danielle C. Cath, Kenji Fukui, Wi Hoon Jung, Sung Nyun Kim, Euripides C. Miguel, Jin Narumoto, Mary L. Phillips, Jesus Pujol, Peter L. Remijnse, Yuki Sakai, Na Young Shin, Kei Yamada, Dick J. Veltman, Odile A. van den Heuvel
Journal: American Journal of Psychiatry (2013)

The effect of persistent symptoms or compensatory processes related to cognitive dysfunction in obsessive-compulsive disorder may contribute to brain structure alterations in OCD, indicating that age is an important factor in evaluating changes in gray and white matter volumes.
Prolonged Remission in a Patient With Nasopharyngeal Carcinoma With a Solitary Bone Metastasis
Authors: Annette Lim, June Corry, Eddie Lau, Danny Rischin
Journal: Journal of Clinical Oncology (2010)

A 24-year-old man presented with a 2-month history of a painlessleftnecklump.Clinicalexaminationrevealeddiffusethickeningof the left neck without a discernable mass and a single right-sided 1.5-cm jugulodigastric node, but no abnormalities elsewhere. Nasendoscopy demonstrated an ulcerated tumor involving bilateral posterior nasopharyngeal walls and roof, blocking the left Eustachian cushion and abutting the right Eustachian cushion. Biopsy of the primary confirmed the diagnosis of nonkeratinising nasopharyngeal carcinoma(NPC),WHOgrade2.Thepatientdeniedanyothersymptomsonfurtherquestioning.HewasofChinese-Malaysianoriginand had lived in Australia from the age of 8 years. He had no significant past medical history, was on no medications, and had no family historyofNPC.Computedtomography(CT)oftheneckconfirmeda nasopharyngeal lesion involving the left torus tuberous, multiple leftsided necrotic lymph nodes and a solitary posterior right triangle lymph node. Chest and abdominal CT did not demonstrate disease elsewhere. He was initially staged as T2 N2 WHO grade 2 NPC. To complete his staging, fused positron emission tomography (PET)/CT was organized, which revealed metabolic avidity in the primary nasopharyngeal lesion (Fig 1A, baseline fused PET/CT axial image of nasopharynx),bilateralcervicalnecknodesasdescribed(Fig1B,baseline
Increased Glutathione and Glutathione Peroxidase in Lungs of Individuals with Chronic Beryllium Disease
Authors: SUZY A. A. COMHAIR, MARC J. LEWIS, PERCY R. BHATHENA, JEFFREY P. HAMMEL, SERPIL C. ERZURUM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Reactive oxygen species (ROS) are mediators of chronic tissue damage and fibrosis. Endogenous antioxidants may increase in response to oxidants and reduce tissue injury. We investigated the antioxidant response of the lungs to the chronic release of ROS, as occurs in the immune-specific granulomatous inflammation of chronic beryllium disease (CBD), and compared it with that in healthy controls and individuals exposed to cigarette smoke. The antioxidants superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione (GSH) were quantitated in lung epithelial lining fluid (ELF) and serum from control subjects (n = 10), cigarette smokers (n = 8), and individuals with CBD (n = 9). GPx activity and extracellular GPx (eGPx) protein were increased in the ELF of subjects with CBD in comparison with that of control subjects and smokers (eGPx in ELF: controls, 1.3 ± 0.2 μ g/ml, smokers, 1.9 ± 0.3 μ g/ml, CBD, 3.8 ± 0.8 μ g/ml; p = 0.002; GPx U/ml ELF, controls 1.4 ± 0.3, smokers 1.8 ± 0.4, CBD, 4.5 ± 1, p = 0.02). Smokers' ELF had higher levels of GSH than that of controls, but CBD patients' ELF contained much more GSH than that of either controls or smokers (p < 0.001). Increases in GSH were correlated with eGPx, indicating similar inducing mechanisms for these antioxidants. Thus, coordinate augmentation of the glutathione antioxidant system occurs in granulomatous lung inflammation.
Impact of Obesity on Cancer Survivorship and the Potential Relevance of Race and Ethnicity
Authors: K. H. Schmitz, M. L. Neuhouser, T. Agurs-Collins, K. A. Zanetti, L. Cadmus-Bertram, L. T. Dean, B. F. Drake
Journal: JNCI Journal of the National Cancer Institute (2013)

Evidence that obesity is associated with cancer incidence and mortality is compelling. By contrast, the role of obesity in cancer survival is less well understood. There is inconsistent support for the role of obesity in breast cancer survival, and evidence for other tumor sites is scant. The variability in findings may be due in part to comorbidities associated with obesity itself rather than with cancer, but it is also possible that obesity creates a physiological setting that meaningfully alters cancer treatment efficacy. In addition, the effects of obesity at diagnosis may be distinct from the effects of weight change after diagnosis. Obesity and related comorbid conditions may also increase risk for common adverse treatment effects, including breast cancer-related lymphedema, fatigue, poor health-related quality of life, and worse functional health. Racial and ethnic groups with worse cancer survival outcomes are also the groups for whom obesity and related comorbidities are more prevalent, but findings from the few studies that have addressed these complexities are inconsistent. We outline a broad theoretical framework for future research to clarify the specifics of the biological-social-environmental feedback loop for the combined and independent contributions of race, comorbid conditions, and obesity on cancer survival and adverse treatment effects. If upstream issues related to comorbidities, race, and ethnicity partly explain the purported link between obesity and cancer survival outcomes, these factors should be among those on which interventions are focused to reduce the burden of cancer.
No more free lunches: Doctors and journals in the South cut off drug companies at their peril
Authors: J. Ana
Journal: BMJ (2003)

EDITOR—Abbasi and Smith raise major ethical issues in their editorial.1 However, the widening gap between the North and the South globally is most glaring in healthcare delivery, training, and information dissemination.

In already rich countries drug companies compete to spend money on doctors and other prescribers, whereas in Africa and most of …
Interleukin 2-induced proliferation of leukemic human B cells.
Authors: O Lantz, C Grillot-Courvalin, C Schmitt, J P Fermand, J C Brouet
Journal: The Journal of Experimental Medicine (1985)

The proliferative responses of purified leukemic human B cells from nine B cell chronic lymphocytic leukemias to recombinant interleukin 2 (IL-2), spontaneously, and after preactivation by Staphylococcus aureus Cowan I (SAC) or anti-mu antibodies were studied. Three patterns of response were observed: (a) no response (three cases); (b) a moderate spontaneous response enhanced by anti-mu (one case); (c) a high proliferative response after preactivation by anti-mu and/or SAC (five cases). IL-2 could also trigger normal B cells, purified from spleen, to proliferative after preactivation by anti-mu or SAC. These results provide evidence that IL-2 is a lymphokine that acts physiologically on both B and T cells.
In Vivo Delivery of Cytoplasmic RNA Virus-derived miRNAs
Authors: Ryan A Langlois, Jillian S Shapiro, Alissa M Pham, Benjamin R tenOever
Journal: Molecular Therapy (2011)

The discovery of microRNAs (miRNAs) revealed an unappreciated level of post-transcriptional control used by the cell to maintain optimal protein levels. This process has represented an attractive strategy for therapeutics that is currently limited by in vivo delivery constraints. Here, we describe the generation of a single-stranded, cytoplasmic virus of negative polarity capable of producing functional miRNAs. Cytoplasmic RNA virus-derived miRNAs accumulated to high levels in vitro, generated significant amounts of miRNA star strand, associated with the RNA-induced silencing complex (RISC), and conferred post transcriptional gene silencing in a sequence-specific manner. Furthermore, we demonstrate that these vectors could deliver miRNAs to a wide range of tissues, and sustain prolonged expression capable of achieving measurable knockdown of physiological targets in vivo. Taken together, these results validate noncanonical processing of cytoplasmic-derived miRNAs and provide a novel platform for small RNA delivery. The discovery of microRNAs (miRNAs) revealed an unappreciated level of post-transcriptional control used by the cell to maintain optimal protein levels. This process has represented an attractive strategy for therapeutics that is currently limited by in vivo delivery constraints. Here, we describe the generation of a single-stranded, cytoplasmic virus of negative polarity capable of producing functional miRNAs. Cytoplasmic RNA virus-derived miRNAs accumulated to high levels in vitro, generated significant amounts of miRNA star strand, associated with the RNA-induced silencing complex (RISC), and conferred post transcriptional gene silencing in a sequence-specific manner. Furthermore, we demonstrate that these vectors could deliver miRNAs to a wide range of tissues, and sustain prolonged expression capable of achieving measurable knockdown of physiological targets in vivo. Taken together, these results validate noncanonical processing of cytoplasmic-derived miRNAs and provide a novel platform for small RNA delivery.
Rebound intragastric hyperacidity after abrupt withdrawal of histamine H2 receptor blockade.
Authors: C U Nwokolo, J T Smith, A M Sawyerr, R E Pounder
Journal: Gut (1991)

<b>Objective:</b> To describe short term patterns of smoking acquisition exhibited by adolescent smokers. <b>Design:</b> Interview records from the prospective development and assessment of nicotine dependence in youth study were examined retrospectively. Interviews were conducted three times per year over 30 months. <b>Subjects:</b> 164 students in grades 7–9 (ages 12–15 years, 86 girls, 78 boys) who had used cigarettes at least twice. <b>Main outcome measures:</b> A continuous timeline of smoking activity, beginning with the subject's first use of tobacco and continuing through follow up, was translated into six patterns—abstinent, sporadic, occasional, daily, escalating, and intermittent. Outcome measures were the proportion of subjects starting/ending in each pattern, and the number of transitions per subject between patterns. <b>Results:</b> There was a general but discontinuous progression from infrequent to more frequent use, with many interspersed periods of not smoking. Escalation to daily smoking was common after the development of dependence symptoms, but was rare among those who did not have symptoms. After the appearance of symptoms, both transitions to heavier daily smoking and attempts at cessation increased. <b>Conclusions:</b> Movement to heavier, more frequent smoking is generally unidirectional, although many youths attempt to quit one or more times. The appearance of any symptom of dependence altered the subsequent pattern of smoking behaviour. Future investigators might consider using more frequent data points and a continuous timeline to track smoking behaviour.
Twist1 expression induced by sunitinib accelerates tumor cell vasculogenic mimicry by increasing the population of CD133+ cells in triple-negative breast cancer
Authors: Danfang Zhang, Baocun Sun, Xiulan Zhao, Yuemei Ma, Ru Ji, Qiang Gu, Xueyi Dong, Jing Li, Fang Liu, Xiaohua Jia, Xue Leng, Chong Zhang, Ran Sun, Jiadong Chi
Journal: Molecular Cancer (2014)

Hypoxia induced by antiangiogenic agents is linked to the generation of cancer stem cells (CSCs) and treatment failure through unknown mechanisms. The generation of endothelial cell-independent microcirculation in malignant tumors is defined as tumor cell vasculogenic mimicry (VM). In the present study, we analyzed the effects of an antiangiogenic agent on VM in triple-negative breast cancer (TNBC). Microcirculation patterns were detected in patients with TNBC and non-TNBC. Tientsin Albino 2 (TA2) mice engrafted with mouse TNBC cells and nude mice engrafted with human breast cancer cell lines with TNBC or non-TNBC phenotypes were administered sunitinib and analyzed to determine tumor progression, survival, microcirculation, and oxygen concentration. Further, we evaluated the effects of hypoxia induced with CoCl2 and the expression levels of the transcription factor Twist1, in the presence or absence of a Twist siRNA, on the population of CD133+ cells and VM in TNBC and non-TNBC cells. VM was detected in 35.8 and 17.8% of patients with TNBC or with non-TNBC, respectively. The growth of tumors in TNBC and non-TNBC-bearing mice was inhibited by sunitinib. The tumors in TA2 mice engrafted with mouse TNBCs and in mice engrafted a human TNBC cell line (MDA-MB-231) regrew after terminating sunitinib administration. However, this effect was not observed in mice engrafted with a non-TNBC tumor cell line. Tumor metastases in sunitinib-treated TA2 mice was accelerated, and the survival of these mice decreased when sunitinib was withdrawn. VM was the major component of the microcirculation in sunitinib-treated mice with TNBC tumors, and the population of CD133+ cells increased in hypoxic areas. Hypoxia also induced MDA-MB-231 cells to express Twist1, and CD133+ cells present in the MDA-MB-231 cell population induced VM after reoxygenation. Moreover, hypoxia did not induce MDA-MB-231 cells transfected with an sh-Twist1 siRNA cell to form VM and generate CD133+ cells. Conversely, hypoxia induced MCF-7 cells transfected with Twist to form VM and generate CD133+ cells. Sunitinib induced hypoxia in TNBCs, and Twist1 expression induced by hypoxia accelerated VM by increasing population of CD133+ cells. VM was responsible for the regrowth of TNBCs sunitinib administration was terminated.
TAXUS I
Authors: Eberhard Grube, Sigmund Silber, Karl Eugen Hauptmann, Ralf Mueller, Lutz Buellesfeld, Ulrich Gerckens, Mary E. Russell
Journal: Circulation (2003)

Background— The TAXUS NIRx stent (Boston Scientific Corp) provides local delivery of paclitaxel via a slow-release polymer coating. The TAXUS I trial was the first in-human experience evaluating safety and feasibility of the TAXUS NIRx stent system compared with bare NIR stents (control) (Boston Scientific Corp) for treatment of coronary lesions. Methods and Results— The TAXUS I trial was a prospective, double-blind, three-center study randomizing 61 patients with de novo or restenotic lesions (≤12 mm) to receive a TAXUS (n=31) versus control (n=30) stent (diameter 3.0 or 3.5 mm). Demographics, lesion characteristics, clinical outcomes were comparable between the groups. The 30-day major adverse cardiac event (MACE) rate was 0% in both groups ( P =NS). No stent thromboses were reported at 1, 6, 9, or 12 months. At 12 months, the MACE rate was 3% (1 event) in the TAXUS group and 10% (4 events in 3 patients) in the control group ( P =NS). Six-month angiographic restenosis rates were 0% for TAXUS versus 10% for control ( P =NS) patients. There were significant improvements in minimal lumen diameter (2.60±0.49 versus 2.19±0.65 mm), diameter stenosis (13.56±11.77 versus 27.23±16.69), and late lumen loss (0.36±0.48 versus 0.71±0.48 mm) in the TAXUS group (all P &lt;0.01). No evidence of edge restenosis was seen in either group. Intravascular ultrasound analysis showed significant improvements in normalized neointimal hyperplasia in the TAXUS (14.8 mm 3 ) group compared with the control group (21.6 mm 3 ) ( P &lt;0.05). Conclusions— In this feasibility trial, the TAXUS slow-release stent was well tolerated and showed promise for treatment of coronary lesions, with significant reductions in angiographic and intravascular ultrasound measures of restenosis.
Promotion of lung cancer progression by COPD-like chronic inflammation in a mouse model
Authors: Fanglei Liu, Qunying Hong, Chunxue Bai
Journal: European Respiratory Journal (2013)

Background:  Chronic inflammation has been suggested as a central role in pathogenesis of lung cancer in COPD patients, the knowledge is still in its infancy. We investigated whether the COPD-like airway inflammation can promote the progression of lung cancer using a COPD mouse model, to demonstrate the role of inflammation in pathogenesis of lung cancer combined with COPD.   Methods:  Adult mouse model of COPD was induced by intratracheal instillation of LPS and exposure to cigarette smoke. To validate this model, we tested the mouse lung function, examined the Lung histology, detected some inflammatory markers in plasma, counted the white cells in BAFL. Then, EGFP-transfected lewis cells were introduced into the lung of COPD mouse and normal mouse by directly puncture through the skin intercostal space. All the mice were scanned by animal fluorescence imaging instrument to observe the progression of lung cancer.   Results:  All the detecting of cigarette smoke and LPS-induced mouse showed that they had features of COPD and chronic inflammation. Compared with the normal mouse, lung cancer in cigarette smoke and LPS-induced mouse developed more quickly and metastasized much earlier. Mouse of COPD combined lung cancer have shorter survival time than those of lung cancer without COPD. IL-6, was significantly higher in the serum of cancer combined with COPD-like mouse model than the COPD-like mouse model and normal mouse.   Conclusions:  We have successfully developed a mouse model with COPD-like airway inflammation. The COPD-like inflammation can promote the progression and metastasis of lung cancer in vivo, and IL-6 may play an important role in this process.
Prediction of Early Death After Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia With Pretreatment Risk Scores: A Novel Paradigm for Treatment Assignment
Authors: Roland B. Walter, Megan Othus, Gautam Borthakur, Farhad Ravandi, Jorge E. Cortes, Sherry A. Pierce, Frederick R. Appelbaum, Hagop A. Kantarjian, Elihu H. Estey
Journal: Journal of Clinical Oncology (2011)

Outcome in acute myeloid leukemia (AML) worsens with age, at least in part because of higher treatment-related mortality (TRM) in older patients. Eligibility for intensive AML treatment protocols is therefore typically based on age as the implied principal predictor of TRM, although other health- and disease-related factors modulate this age effect.We empirically defined TRM using estimated weekly hazard rates in 3,365 adults of all ages administered intensive chemotherapy for newly diagnosed AML. We used the area under the receiver operator characteristic curve (AUC) to quantify the relative effects of age and other covariates on TRM in a subset of 2,238 patients. In this approach, an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is analogous to a coin flip.Regardless of age, risk of death declined once 4 weeks had elapsed from treatment start, suggesting that patients who die during this time comprise a qualitatively distinct group. Performance status (PS) and age were the most important individual predictors of TRM (AUCs of 0.75 and 0.65, respectively). However, multicomponent models were significantly more accurate in predicting TRM (AUC of 0.83) than PS or age alone. Elimination of age from such multicomponent models only minimally affected their predictive accuracy (AUC of 0.82).These data suggest that age is primarily a surrogate for other covariates, which themselves add significantly to predictive accuracy, thus challenging the wisdom of using age as primary or sole basis for assignment of intensive, curative intent treatment in AML.