tbuckley/cabot-search huggingface dataset:
Clinical significance of chemotherapy for small cell lung cancer (SCLC) with ECOG performance status (PS) 3–4
Authors: H. Kenmotsu, K. Goto, K. Kubota, H. Ohmatsu, S. Niho, K. Yoh, N. Saijo, Y. Nishiwaki
Journal: Journal of Clinical Oncology (2008)

19123 Background: There are few reports which show the efficacy of chemotherapy for SCLC in the patients with PS 3–4. Methods: To assess the efficacy and feasibility of chemotherapy for SCLC with poor PS, we retrospectively reviewed the outcome for 48 SCLC patients with PS 3–4 received chemotherapy at National Cancer Center East between July 1992 and May 2007. The improvement rate of PS (two or more levels improvement) and the overall survival were compared by means of chi-square test and log-rank test, respectively. Results: Patient characteristics of 48 SCLC were median age 66 (range 53–81), M/F: 42/6, PS3/4: 41/7, and limited disease (LD) /extensive disease (ED): 12/36. As first-line chemotherapy, 22 patients were treated with carboplatin plus etoposide, 15 with CODE (weekly administration of cisplatin, vincristine, doxorubicin and etoposide), 9 with cisplatin plus etoposide, 2 patients with others. Median follow-up time was 6.6 months. The overall response rate was 58%, median survival time was 3.6 months, and PS improvement rate was 48%. Patients with serum albumin level > 3.0 g/dL showed significantly better survival time (median 5.5 months vs 1.6 months, p < 0.01) and PS improvement rate (59% vs 21%, p = 0.02). In addition, platelet counts ≥ 1.0×105/μL (p < 0.01) or LD (p < 0.01) were significantly correlated with overall survival. The grade 3/4 neutropenia, thrombocytopenia, febrile neutropenia were observed in 65%, 40%, 42%, respectively. Thirteen patients died within one month after the start of chemotherapy. Conclusion: SCLC patients with PS 3–4 had poor prognosis. However, since serum albumin level, platelet counts, and LD were significantly correlated with better survival or PS improvement rate, it is estimated that PS 3–4 patients with one of these factors might be candidate for intensive chemotherapy. No significant financial relationships to disclose.
Abstract 76: Early Institution of Hypothermic Total Liquid Ventilation After Prolonged Cardiac Arrest Protects Against Kidney Ischemic Alterations
Authors: Renaud Tissier, Sébastien Giraud, Nathalie Quellard, Béatrice Fernandez, Jean-Michel Goujon, Fanny Lidouren, Lys Darbera, Matthias Kohlhauer, Mourad Chenoune, Patrick Bruneval, Bijan Ghaleh, Alain Berdeaux, Thierry Hauet
Journal: Circulation (2012)

Introduction: Warm ischemia before organ removal is a major cause of kidney alterations in transplants from non-heart-beating donors. In a rabbit model of cardiac arrest (CA), we showed that rapid cooling using total liquid ventilation (TLV) can improve survival and protect heart and brain after resuscitation. Hypothesis: We hypothesized that TLV with perfluorocarbons can also limits kidney alterations after CA, with potential applications for controlled organ donation in the Maastricht III category. Methods: Anesthetized rabbits were submitted to 15 min of untreated ventricular fibrillation. After resuscitation and resumption of spontaneous circulation (ROSC), rabbits underwent Control life support or hypothermia (32-33°C) induced by TLV and maintained with external blankets under mechanical ventilation. Life support was prolonged during 6 h before kidney removal and analysis. Other rabbits were submitted to similar follow-up with no CA (Sham group). Results: In each group, 8 animals completed the protocol. Despite similar delays before ROSC (∼4 min), epinephrine doses required to maintain blood pressure throughout follow-up were lower in TLV vs Control (361±23 vs 990±179 µg/kg, respectively). This was accompanied by a decrease in creatinine blood levels after CA (12±1 vs 16±2 mg/l), while still altered when compared to Sham values (8±1 mg/l). Importantly, kidney lesions were also attenuated in TLV vs Control (Figure). The nephroprotective effect of TLV was not related to differences in delayed inflammatory or immune renal responses since transcriptions of, e.g., IFN-γ, TNF-α, IL-1β, MCP-1, TLR-2, TLR-4, VEGF, ICAM-1 and E-selectin were similarly altered in TLV and Control vs Sham. An immediate anti-ischemic effect of rapid cooling with TLV might accordingly be involved. Conclusion: Ultra-fast cooling with TLV limits kidney alterations after prolonged experimental CA. *, p&lt;0.05 vs Sham; †, p&lt;0.05 vs Control.
Binding of the Active Vitamin A Metabolite Retinoic Acid to the Major Cows Milk Allergen Bos d 5 Down-Regulates T-Cell Responses
Authors: Stefanie Wagner, Karin Hufnagl, Luis F.F. Pacios, Franziska Roth-Walter, Rodolfo Bianchini, Gerlinde Hofstetter, Erika Jensen-Jarolim
Journal: Journal of Allergy and Clinical Immunology (2016)
Phase Ib study of PGG beta glucan in combination with anti-MUC1 antibody (BTH1704) and gemcitabine for the treatment of advanced pancreatic cancer.
Authors: Neeta K. Venepalli, Chintan Chandrakant Gandhi, Howard Ozer, Dominic Ho, Yang Lu, Hui Xie, Stephanie A. Berg, Rozina A. Chowdhery, Michele Anne Gargano, Ada H. Braun, Arkadiusz Z. Dudek
Journal: Journal of Clinical Oncology (2015)

TPS493 Background: Mucin 1 (MUC1) is a tumor associated membrane-bound glycoprotein that promotes oncogenesis through promotion of epithelial cell polarity loss, anti-apoptosis, and hypoxia driven angiogenesis. MUC1 overexpression is associated with aggressive behavior and poor outcomes in pancreatic ductal adenocarcinoma (PDAC), and increased resistance to gemcitabine (G) in vitro. BTH1704 (BTH) is a humanized monoclonal antibody (MAb) targeting aberrantly glycosylated MUC1. Imprime PGG (PGG) is a soluble yeast-derived b 1,3/1,6 glucan that binds complement receptor 3 (CR3) on innate immune cells priming them to exert anti-tumor activity against complement (iC3b) opsonized tumor cells. Following incubation of PGG with whole blood from healthy subjects, variability in PGG binding to neutrophils and monocytes has been observed, with higher binding and functional changes correlating with higher levels of endogenous anti-b glucan antibodies. BTH binds to antigens (MUC1), leading to iC3b opsonization of tumor cells thus, allowing PGG-primed leukocytes to kill the iC3b-opsonized tumor cells. This forms the rationale for testing BTH1704 combined with G + PGG. Methods: This is a single institution Phase 1b dose escalation study with a standard 3x3 design to determine the maximal administered dose (MAD) of BTH combined with G + PGG in patients with previously treated advanced PDAC.Each dose cohort includes at least one subject with high and one low PGG binding capability. Primary objectives: establish MAD of BTH combined with G + PGG. Secondary objectives: characterize adverse effects, clinical response, time to progression, progression free and overall survival. Correlative objectives: quantify PGG binding, MDSC phenotyping of PBMC, anti b glucan antibody levels, MUC1 IHC. Inclusion criteria: confirmed advanced PDAC, ECOG PS 0-2, rest period 2-6 weeks from prior first- or second-line treatment. Exclusion criteria: uncontrolled chronic illness. Administration and design: BTH and PGG are administered on days 1, 8, 15, and 22 of a 28-day cycle; G is administered on days 1, 8, and 15. The study is currently enrolling patients. Clinical trial information: NCT02132403. Clinical trial information: NCT02132403.
A Randomized Study to Determine the Optimal Dose of Darbepoetin Alfa in Patients with Low- or Intermediate-1 Risk Myelodysplastic Syndromes
Authors: Hironori Harada, Hirohiko Shibayama, Jun Ho Jang, Ryutaro Shimazaki, Kinuko Mitani, Kenichi Sawada, Hyeoung-Joon Kim
Journal: Blood (2014)
Randomized study of early intervention compared to standard intervention with darbepoetin-alpha (DA) for chemotherapy-induced anemia (CIA) in early stage breast cancer (ESBC)
Authors: L. Blakely, L. S. Schwartzberg, D. Henry, K. Sabbath, D. Fu, A. Epperson, B. V. Fortner
Journal: Journal of Clinical Oncology (2007)

19538 Background: Dose dense chemotherapy (DDC) with sequential doxorubicin/ cyclophosphamide followed by paclitaxel Q 14 days has an established place in the treatment of ESBC. However, moderate/severe CIA is a common consequence and therapeutic intervention is frequent. We sought to determine if early intervention at the onset of anemia with DA could reduce the emergence of more severe anemia during therapy and maintain quality of life compared to later intervention. Material and Methods: Non-iron deficient (ferritin &gt; 50) patients (pts) with hemoglobin (Hb) levels &gt;11.0 g/dl scheduled to receive adjuvant or neoadjuvant DDC for ESBC were recruited. Pts were randomly assigned prior to chemotherapy to initiate treatment with DA 200 μg q2w SQ when Hb &lt; 11.5 g/dl (early intervention, EARLY), or DA 200 μg q2w SQ when Hb &lt; 10.0 g/dl (standard intervention, STD) with end of treatment defined as 14 days after the last cycle of chemotherapy. Dose escalation for inadequate response of &lt; 1 g/dl after 6 weeks of DA and dose withholding/reduction for Hb &gt;13 g/dl were pre-specified. Results: The complete sample of 149 pts have been accrued (median age of 53.1, range 28.7 - 74.5). Analysis of fatigue ratings show a trend towards lower fatigue scores in EARLY at Hb nadir, and at end of study,(ANOVA, Group x Time interaction, p=.07). Discussion: Early intervention with DA significantly reduces the risk of developing moderate/severe CIA and increases time spent in the target range during DDC for ESBC. [Table: see text] No significant financial relationships to disclose.
Effect of hypothalamic/pituitary radiation exposure in low doses on fertility in female childhood cancer survivor study (CCSS) participants.
Authors: D. M. Green, V. G. Nolan, T. Kawashima, M. Stovall, S. S. Donaldson, C. A. Sklar, L. L. Robison
Journal: Journal of Clinical Oncology (2010)

9542 Background: Female childhood cancer survivors (CCS) are less likely to report having been pregnant when compared with females within the CCSS sibling cohort (Sibs) as the result of direct damage to the ovaries produced by radiation therapy (XRT) and/or chemotherapy. High-dose hypothalamic/pituitary (HPT) XRT, which causes central or secondary hypogonadism, may result in infertility due to failure to stimulate ovulation. Recently, another possible central mechanism has been postulated, luteal phase deficiency, resulting from low-dose HPT XRT. Methods: We evaluated the occurrence of pregnancy in 3,666 female CCS who participated in the CCSS and 2,082 Sibs. The association between low- dose HPT XRT and fertility was studied by restricting analyses to those female CCS who received no/scatter (≤10 cGy) radiation to the ovaries and comparing their fertility rates with those of Sibs using Cox-proportional hazards models. Specific treatment effects were studied by further limiting analyses to only CCS. Results: These CCS who received no/scatter (≤ 10 cGy) ovarian radiation were more likely to report being pregnant (hazard ratio [HR]:1.5, 95% confidence interval [95%CI]: 1.3, 1.7) when adjusted for race/ethnicity, smoking, marital status, and education than Sibs. Multivariable models showed a significant decrease in the risk of reporting pregnancy with HPT XRT doses of ≥ 2,200 cGy when compared with those CCS receiving no HPT XRT when adjusted for race/ethnicity, smoking, marital status, education, age at diagnosis, and treatment with VP16 (Table) (137 had missing HPT radiation doses). Conclusions: The results of this study support the hypothesis that low-dose HPT XRT may be a contributing factor to infertility among female CCS. HPT radiation dose (cGy) Number of CCSS participants HR ever pregnant 95% CI ever pregnant 0 1,996 1.0 > 0 to < 1500 371 0.8 0.7-1.1 ≥ 1500 to < 2200 599 0.9 0.7-1.1 ≥ 2200 to < 2700 316 0.6 0.5-0.8 ≥ 2700 247 0.7 0.5-0.9 No significant financial relationships to disclose.
Leukemic Cellular Retinoic Acid Resistance and Missense Mutations in the PML-RAR Fusion Gene After Relapse of Acute Promyelocytic Leukemia From Treatment With All-trans Retinoic Acid and Intensive Chemotherapy
Authors: Wei Ding, Yun-Ping Li, Lucio M. Nobile, George Grills, Ines Carrera, Elisabeth Paietta, Martin S. Tallman, Peter H. Wiernik, Robert E. Gallagher
Journal: Blood (1998)
Long-term Impact of Mode of Delivery on Stress Urinary Incontinence and Urgency Urinary Incontinence: A Systematic Review and Meta-analysis
Authors: Riikka M. Tähtinen, Rufus Cartwright, Johnson F. Tsui, Riikka L. Aaltonen, Yoshitaka Aoki, Jovita L. Cárdenas, Regina El Dib, Kirsi M. Joronen, Sumayyah Al Juaid, Sabreen Kalantan, Michal Kochana, Malgorzata Kopec, Luciane C. Lopes, Enaya Mirza, Sanna M. Oksjoki, Jori S. Pesonen, Antti Valpas, Li Wang, Yuqing Zhang, Diane Heels-Ansdell, Gordon H. Guyatt, Kari A.O. Tikkinen
Journal: European Urology (2016)

Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain. To investigate the long-term impact of delivery mode on SUI and UUI. We searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias. Pooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56–2.19; I2 = 57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p = 0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84–1.45; I2 = 50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02–1.65; I2 = 37%; risk difference: 2.6%). Compared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%. In this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.
Was Committee on Safety of Medicines' advice arrived at lawfully?
Authors: A. H Watt
Journal: BMJ (1995)

progestogens desogestrel and gestodene.Rawlins claims that the committee has to take on the responsibilities of peer reviewers with regard to unpublished information.2In this it presumes to act as both judge and jury, a single role that the United States Food and Drug Administration rightly refuses to assume.Presented with similar problems, the administration embarks on detailed public hearings, with the eventual publication of a comprehensive report.3The necessity for such
Adhesion and Migration Are Differentially Regulated in Hematopoietic Progenitor Cells by Cytokines and Extracellular Matrix
Authors: Eva-Susanne Strobel, Dieter Möbest, Sabine von Kleist, Matthias Dangel, Stefan Ries, Roland Mertelsmann, Reinhard Henschler
Journal: Blood (1997)

Abstract The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin−Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on β1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF ), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF ), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1α, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-β1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that β1-integrin–mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of β1-integrins in hematopoietic progenitor cells.
Geographic variation in patient surveillance after colon cancer surgery.
Authors: F E Johnson, L W McKirgan, M A Coplin, A M Vernava, W E Longo, T P Wade, K S Virgo
Journal: Journal of Clinical Oncology (1996)

Considerable variation among surgeons exists in the current practice of patient surveillance after colon cancer treatment. We evaluated whether geographic factors are responsible for this observed variation.Profiles of hypothetical patients and a detailed questionnaire based on the profiles were mailed to 2,733 members of two national surgical societies. The influence of the geographic location of the respondents on practice patterns were assessed in two ways. Repeated-measures analysis of variance was used to compare the practice patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis was used to determine whether these patterns differed by MSA population size.Seven of nine commonly used surveillance modalities were ordered significantly more frequently with increasing tumor-node-metastasis (TNM) stage and significantly less frequently with year postsurgery among the 995 respondents with assessable responses, but MSA population size and geographic location of physicians generally had no effect on documented practice variability. The remaining two modalities (bone scan and computed tomography [CT]) were used so infrequently as to preclude meaningful analysis.Surveillance after potentially curative colon cancer surgery for otherwise healthy patients is not significantly affected by the geographic location of the surgeon who performs the surveillance testing and only modestly affected by the population size of the MSA in which he/she practices. These data should help in the design of prospective trials of this topic.
The Evolution and Significance of the Modern Public Health Campaign.
Journal: JAMA (1924)

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Microarray gene expression analysis of fatty acid synthase (FAS) signaling on breast cancer cell lines
Authors: A. Vazquez-Martin, G. Moreno, R. Colomer, J. A. Menendez, S. Ropero, C. Oliveras, J. Palacios
Journal: Journal of Clinical Oncology (2004)

9690 Background: Fatty acid synthase (FAS) is the enzyme responsible for the de novo synthesis of fatty acids, and is overexpressed in 20% of human breast carcinomas. The inhibition of FAS induces apoptosis, and has shown significant antitumor activity against human breast, prostate and ovarian cancer xenografts. We have previously observed that inhibition of FAS acts synergistically with trastuzumab inhibiting the proliferation of HER2-positive, FAS positive breast cancer cells. We have also shown that inhibition of FAS enhances the effectiveness of paclitaxel, docetaxel and vinorelbine, and reverses anthracyclin resistance on breast cancer cells. We have now tested the effects of cerulenin, an inhibitor of FAS, on gene expression analysis of the breast cancer cell lines SK-Br-3, BT-474, and MCF-7, which express different levels of FAS (++, +, and negative). Methods: Using 10,000-spot human cDNA microarrays, we have evaluated the time course of the transcriptional response of breast cancer cells to FAS inhibition (6 to 24h). Results: Gene response paralelled the magnitude and time-course of FAS enzymatic inhibition. In FAS-positive cells, significant up-regulation (>6-fold) was observed for osteonectin, TGF-β2, and genes involved in the insulin signalling pathway (IGFBP-1, IGFBP-2, IGFBP-3 and IGF5), apoptosis (caspase-7, Gas-7, Gas-1), and metastasis inhibition (thrombospondin, osteoprotegirin, kiss-1). Significant down-regulation (>6-fold) was observed for Grb7 (involved in HER2-signalling pathway), FGF5, inhibin, and IL-11. Conclusions: The observed changes on the gene expression pattern provide new insights in the molecular mechanisms of the inhibition of FAS, and will help in the development of new inhibitory molecules. No significant financial relationships to disclose.