tbuckley/cabot-search huggingface dataset:
Trimodality Therapy With Induction Chemotherapy Followed by Extrapleural Pneumonectomy and Adjuvant High-Dose Hemithoracic Radiation for Malignant Pleural Mesothelioma
Authors: Marc de Perrot, Ronald Feld, B.C. John Cho, Andrea Bezjak, Masaki Anraku, Ronald Burkes, Heidi Roberts, Ming S. Tsao, Natasha Leighl, Shaf Keshavjee, Michael R. Johnston
Journal: Journal of Clinical Oncology (2009)

Malignant pleural mesothelioma (MPM) remains associated with poor outcome. We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy (EPP) and adjuvant high-dose (50 to 60 Gy) hemithoracic radiation therapy for MPM.We conducted a retrospective review of all patients prospectively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution.A total of 60 patients were suitable candidates. Histology was epithelioid (n = 44) or biphasic (n = 16). Chemotherapy regimens included cisplatin/vinorelbine (n = 26), cisplatin/pemetrexed (n = 24), cisplatin/raltitrexed (n = 6), or cisplatin/gemcitabine (n = 4). EPP was performed in 45 patients, and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients. Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival (median survival of 59 months v <or= 14 months in the remaining patients, P = .0003). The type of induction chemotherapy had no significant impact on survival. Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy. After completion of the protocol, the 5-year disease-free survival was 53% for patients with N0 disease, reaching 75% in patients with ypT1-2N0 and 45% in patients with ypT3-4N0.This large, single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol. The results are encouraging for patients with N0 disease. However, N2 disease remains a major factor impacting on survival, despite completion of the entire trimodality regimen.
The Context of Blood Vessels and Response to VEGF-Targeted Therapy
Authors: Brian I. Rini
Journal: Clinical Cancer Research (2013)

Abstract Although therapy directed against VEGF has produced clinical benefit, an understanding of responsive tumor characteristics is lacking. Blood vessel location relative to tumor cells and stromal factors may influence tumor susceptibility to VEGF-targeted therapy. Clinical validation of this potential biomarker is needed to influence clinical practice. Clin Cancer Res; 19(24); 6647–9. ©2013 AACR.
Ancestral Effect on HOMA-IR Levels Quantitated in an American Population of Mexican Origin
Authors: Hui-Qi Qu, Quan Li, Yang Lu, Craig L. Hanis, Susan P. Fisher-Hoch, Joseph B. McCormick
Journal: Diabetes Care (2012)

OBJECTIVE An elevated insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) is more commonly seen in the Mexican American population than in European populations. We report quantitative ancestral effects within a Mexican American population, and we correlate ancestral components with HOMA-IR. RESEARCH DESIGN AND METHODS We performed ancestral analysis in 1,551 participants of the Cameron County Hispanic Cohort by genotyping 103 ancestry-informative markers (AIMs). These AIMs allow determination of the percentage (0–100%) ancestry from three major continental populations, i.e., European, African, and Amerindian. RESULTS We observed that predominantly Amerindian ancestral components were associated with increased HOMA-IR (β = 0.124, P = 1.64 × 10−7). The correlation was more significant in males (Amerindian β = 0.165, P = 5.08 × 10−7) than in females (Amerindian β = 0.079, P = 0.019). CONCLUSIONS This unique study design demonstrates how genomic markers for quantitative ancestral information can be used in admixed populations to predict phenotypic traits such as insulin resistance.
1203 SAFETY PROFILE OF DACLATASVIR IN COMBINATION WITH PEGINTERFERON alfa AND RIBAVIRIN IN 1100 PATIENTS WITH CHRONIC HCV INFECTION TREATED IN PHASE 2 STUDIES
Authors: I. Jacobson, D. Dimitrova, E.A. Hughes, P.D. Yin, P. Mendez, L. Yogendran, S. Schnittman
Journal: Journal of Hepatology (2013)
373 WHAT ARE THE APPROPRIATE INDICATIONS OF RESECTION AND TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA (HCC)?
Authors: K. Hasegawa, Y. Sugawara, S. Tamura, T. Aoki, J. Kaneko, T. Ishizawa, Y. Inoue, M. Takahashi, H. Imamura, Y. Beck, M. Makuuchi, N. Kokudo
Journal: Journal of Hepatology (2008)
Cardiotoxicity of Epirubicin/Paclitaxel–Containing Regimens: Role of Cardiac Risk Factors
Authors: Alessandra Gennari, Barbara Salvadori, Sara Donati, Carmelo Bengala, Cinzia Orlandini, Romano Danesi, Mario Del Tacca, Paolo Bruzzi, Pier Franco Conte
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the incidence of clinically relevant cardiac toxicity after treatment with epirubicin/paclitaxel-containing regimens in patients with metastatic breast cancer and to identify high-risk patients in whom the benefit of chemotherapy may be negated by the occurrence of congestive heart failure (CHF). PATIENTS AND METHODS: A total of 105 patients who were referred for epirubicin/paclitaxel treatment were included in this study. Treatment regimens were as follows: (1) epirubicin 90 mg/m 2 plus paclitaxel 135 to 225 mg/m 2 over 3 hours (n = 76); and (2) gemcitabine 1,000 mg/m 2 on days 1 and 4 plus epirubicin/paclitaxel (n = 29). The occurrence of CHF was detected by physical examination, and left ventricular function was evaluated by bidimensional echocardiography to support the diagnosis. Cardiac risk factors examined in this study included age, prior radiotherapy to the chest, hypertension, and diabetes. RESULTS: No patient experienced CHF while on treatment. Nine patients (9%) developed CHF after cumulative epirubicin doses of 1,080 mg/m 2 (n = 4), 720 mg/m 2 (n = 2), 630 mg/m 2 (n = 1), and 540 mg/m 2 (n = 2). One of the two patients who developed CHF after a cumulative epirubicin dose of 540 mg/m 2 had received consolidation with high-dose chemotherapy. Median time to appearance of cardiologic symptoms was 3 months after the end of treatment (range, 3 to 6 months). Overall, the incidence of CHF was 13% and 4% in patients with or without cardiac risk factors, respectively. The cumulative risk of developing CHF was estimated as 7.7% at a cumulative doses of 720 mg/m 2 and 48.7% at a cumulative dose of 1,080 mg/m 2 . CONCLUSION: This study shows that the incidence of CHF after an epirubicin/paclitaxel regimen is low up to cumulative epirubicin doses of 990 mg/m 2 , thus allowing the safe administration of this regimen even in patients who received epirubicin in the adjuvant setting. However, the risk of developing CHF increases when a cumulative dose exceeding 990 mg/m 2 is reached, concomitantly with the presence of an additional cardiac risk factor.
Thymoma Complicated by Acquired Amegakaryocytic Thrombocytopenia and Pure Red Cell Aplasia
Authors: Carl M. Gay, William N. William, Sa A. Wang, Thein Hlaing Oo
Journal: Journal of the National Comprehensive Cancer Network (2014)

Although the association of pure red cell aplasia (PRCA) and aplastic anemia with thymoma is well-known, acquired amegakaryocytic thrombocytopenia (AAMT) is not a recognized paraneoplastic manifestation of thymoma. This report discusses a patient with recurrent thymoma complicated by myasthenia gravis, PRCA, and AAMT. Both PRCA and AAMT are diagnosed after a thymoma recurrence, 11 years after complete resection of the initial tumor and 9 months after chemotherapy for the relapsed disease. Both PRCA and AAMT responded to immunosuppression with cyclosporine, corticosteroid, and an abbreviated course of antithymocyte globulin, achieving a very good erythroid response and a complete remission for AAMT, suggesting that AAMT, although extremely rare, can be an immune-mediated paraneoplastic manifestation of thymoma.
Observations on iron in the jejunal lumen after a standard meal
Authors: J. Glover, A. Jacobs
Journal: Gut (1971)

For two hours after the ingestion of a standard meal with an iron content of 3.45 mg there is a rise in iron concentration in the jejunal lumen. Initially this is in a high molecular weight form but there is a steady increase in the concentration of low molecular weight compounds. This is consistent with the gradual intraluminal transfer of iron from a mucopolysaccharide carrier to low molecular weight ligands before absorption.
Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis
Authors: Danielle Califano, Keith J. Sweeney, Hung Le, Jeffrey VanValkenburgh, Eric Yager, William O’Connor, Jeffrey S. Kennedy, David M. Jones, Dorina Avram
Journal: Journal of Clinical Investigation (2013)

Naive T helper cells differentiate into functionally distinct effector subsets that drive specialized immune responses. Recent studies indicate that some of the effector subsets have plasticity. Here, we used an EAE model and found that Th17 cells deficient in the transcription factor BCL11B upregulated the Th2-associated proteins GATA3 and IL-4 without decreasing RAR-related orphan receptor γ (RORγt), IL-17, and GM-CSF levels. Surprisingly, abnormal IL-4 production affected Th17 cell trafficking, diverting migration from the draining lymph nodes/CNS route to the mesenteric lymph nodes/gut route, which ameliorated EAE without overt colitis. T helper cell rerouting in EAE was dependent on IL-4, which enhanced retinoic acid (RA) production by dendritic cells, which further induced expression of gut-homing receptors CCR9 and α4β7 on Bcl11b-deficient CD4+ T cells. Furthermore, IL-4 treatment or Th2 immunization of wild-type mice with EAE caused no alteration in Th17 cytokines or RORγt, but diverted T helper cell trafficking to the gut, which improved EAE outcome without overt colitis. Our data demonstrate that Th17 cells are permissive to Th2 gene expression without affecting Th17 gene expression. This Th17 plasticity has an impact on trafficking, which is a critical component of the immune response and may represent a possible avenue for treating multiple sclerosis.
Is Endometrial Cancer Risk Reduced by Oral Bisphosphonate Use?
Authors: Federica Tomao, Nicoletta Colombo, Benedetti Panici
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: We analyzed the results from the study published in Journal of Clinical Oncology by Newcomb et al. The topic is interesting and the conclusions, attractive. The authors carefully controlled participants from the Women’s Health Initiative for weight and body mass index but did not assess some anamnestic confounding data of great relevance. In the exclusion section of the study, they declared that women with a history of antiestrogen use were excluded from analyses. However, they did not report data about previous use of other hormonal agents capable of reducing the production and effects of endogenous estrogens. Gonadotropin-releasing hormone analogs, oral contraceptives, and progestins are widely used in clinical practice for contraception and treatment of benign gynecologic diseases, such as endometriosis, polyps, uterine fibromatosis, and menstrual-cycle disorders. All of these treatments can lower the risk of endometrial cancer, mainly in the case of long-term therapy. Moreover, previous use of statins was not reported in the article, although these drugs have demonstrated preventive effect in endometrial cancer. Use of these agents is frequent in clinical practice, mainly in postmenopausal women. Therefore, they represent a possible factor that may influence the incidence of endometrial cancer in the population that Newcomb et al studied. Although recent data have confirmed the result from the study by Newcomb et al, we believe that the protective use of bisphosphonates for the prevention of endometrial cancer is suggestive but still not conclusive.
Renal Expression of the Ets-1 Proto-oncogene during Progression of Rat Crescentic Glomerulonephritis
Authors: TAKASHI NAITO, MOHAMMED S. RAZZAQUE, ARIFA NAZNEEN, DIANGE LIU, HIROSHI NIHEI, TAKEHIKO KOJI, TAKASHI TAGUCHI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The ets-1 proto-oncogene is a member of the transcriptional factor family and was identified by homology to the v-ets oncogene. It was recently demonstrated that Ets-1 protein interacts with the promoter region of the genes coding for proteinases, including matrix metalloproteinase-1 (MMP-1), MMP-3, and urokinase-type plasminogen activator, suggesting that it may play an important role in the regulation of MMP expression. The role of the ets-1 proto-oncogene in advanced glomerular diseases, where extracellular matrix accumulation is observed, remains undefined. In this study, the expression of ets-1 mRNA and protein during the progression of rat crescentic glomerulonephritis was examined using immunohistochemical analysis, reverse transcription-PCR, and in situ hybridization. Passive accelerated anti-glomerular basement membrane-induced nephritis was induced in rats by intravenous injection of nephrotoxic serum. Rats were euthanized on day 7, 14, 21, 28, or 42. Immunohistochemical analysis demonstrated significant upregulation of Ets-1 protein expression in glomeruli and the interstitium in anti-glomerular basement membrane-induced nephritis. The numbers of Ets-1-positive cells were increased 8.8-fold on day 21 in glomeruli (1.2 ± 0.1 cells/glomerular cross-section, P < 0.001) and sixfold on day 28 in the interstitium (21 ± 1.3 cells/mm2, P < 0.001), compared with control samples. Ets-1 protein was predominantly localized in glomerular epithelial cells, endothelial cells, and interstitial cells. A small number of vascular endothelial cells, macrophages, and T cells also expressed Ets-1 protein. MMP-3 deposition was upregulated and positive cells in the interstitium often coexpressed Ets-1, whereas only a few glomerular cells were positive for both MMP-3 and Ets-1 protein. The expression of ets-1 mRNA was also markedly increased in diseased kidneys. The distribution of ets-1 mRNA was similar to that of the protein. These results indicate that overexpression of the ets-1 proto-oncogene by phenotypically altered renal cells might be associated with the pathogenesis of rat crescentic glomerulonephritis.
Thymus-autonomous T cell development in the absence of progenitor import
Authors: Vera C. Martins, Eliana Ruggiero, Susan M. Schlenner, Vikas Madan, Manfred Schmidt, Pamela J. Fink, Christof von Kalle, Hans-Reimer Rodewald
Journal: The Journal of Experimental Medicine (2012)

Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell–deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2−/−γc−/−KitW/Wv mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2−/−γc−/−KitW/Wv hosts, γc-mediated signals alone played a key role in the competition between thymus-resident and bone marrow–derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus.
Progression-Free Survival as a Predictor of Overall Survival in Men With Castrate-Resistant Prostate Cancer
Authors: Susan Halabi, Nicholas J. Vogelzang, San-San Ou, Kouros Owzar, Laura Archer, Eric J. Small
Journal: Journal of Clinical Oncology (2009)

To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer.Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS.The median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32).PFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.
Interleukin 12 (IL-12) Is Crucial to the Development of Protective Immunity in Mice Intravenously Infected with <i>Mycobacterium tuberculosis</i>
Authors: Andrea M. Cooper, Jeanne Magram, Jessica Ferrante, Ian M. Orme
Journal: The Journal of Experimental Medicine (1997)

Immunity to Mycobacterium tuberculosis infection is associated with the emergence of protective CD4 T cells that secrete cytokines, resulting in activation of macrophages and the recruitment of monocytes to initiate granuloma formation. The cytokine-mediating macrophage activation is interferon-γ (IFN-γ), which is largely dependent on interleukin-12 (IL-12) for its induction. To address the role of IL-12 in immunity to tuberculosis, IL-12 p40−/− mice were infected with M. tuberculosis and their capacity to control bacterial growth and other characteristics of their immune response were determined. The IL-12 p40−/− mice were unable to control bacterial growth and this appeared to be linked to the absence of both innate and acquired sources of IFN-γ. T cell activation as measured by delayed type hypersensitivity and lymphocyte accumulation at the site of infection were both markedly reduced in the IL-12 p40−/− mice. Therefore, IL-12 is essential to the generation of a protective immune response to M. tuberculosis, with its main functions being the induction of the expression of IFN-γ and the activation of antigen-specific lymphocytes capable of creating a protective granuloma.
Single cell transcriptomics of neighboring hyphae of Aspergillus niger
Authors: Charissa de Bekker, Oskar Bruning, Martijs J Jonker, Timo M Breit, Han AB Wösten
Journal: Genome biology (2011)

Abstract Single cell profiling was performed to assess differences in RNA accumulation in neighboring hyphae of the fungus Aspergillus niger . A protocol was developed to isolate and amplify RNA from single hyphae or parts thereof. Microarray analysis resulted in a present call for 4 to 7% of the A. niger genes, of which 12% showed heterogeneous RNA levels. These genes belonged to a wide range of gene categories.
Randomized Trial of Induction Chemotherapy With Cisplatin and 5-Fluorouracil With or Without Docetaxel for Larynx Preservation
Authors: Y. Pointreau, P. Garaud, S. Chapet, C. Sire, C. Tuchais, J. Tortochaux, S. Faivre, S. Guerrif, M. Alfonsi, G. Calais
Journal: JNCI Journal of the National Cancer Institute (2009)

Chemotherapy with cisplatin (P) and 5-fluorouracil (F) followed by radiotherapy in patients who respond to chemotherapy is an alternative to total laryngectomy for patients with locally advanced larynx and hypopharynx cancer. Data suggest that docetaxel (T) may add to the efficacy of PF. The objective of this trial was to determine whether adding T to PF could increase the larynx preservation rate. Patients who had larynx and hypopharynx cancer that required total laryngectomy were randomly assigned to receive three cycles of TPF or PF. Patients who responded to chemotherapy received radiotherapy with or without additional chemotherapy. Patients who did not respond to chemotherapy underwent total laryngectomy followed by radiotherapy with or without additional chemotherapy. The primary endpoint was 3-year larynx preservation rate. Secondary endpoints included acute toxicities and overall response. All statistical tests were two-sided. Baseline patient and tumor characteristics were well balanced between the TPF (n = 110) and PF (n = 103) groups. With a median follow-up of 36 months, the 3-year actuarial larynx preservation rate was 70.3% with TPF vs 57.5% with PF (difference = 12.8%; P = .03). Patients in the TPF group had more grade 2 alopecia, grade 4 neutropenia, and febrile neutropenia, whereas patients in the PF group had more grade 3 and 4 stomatitis, thrombocytopenia, and grade 4 creatinine elevation. The overall response was 80.0% in the TPF group vs 59.2% in the PF group (difference = 20.8%; P = .002). In patients with advanced larynx and hypopharynx carcinomas, TPF induction chemotherapy was superior to the PF regimen in terms of overall response rate. These results suggest that larynx preservation could be achieved for a higher proportion of patients.
Respiratory Muscle Dysfunction in Congestive Heart Failure
Authors: F. Joachim Meyer, Mathias M. Borst, Christian Zugck, Andreas Kirschke, Dieter Schellberg, Wolfgang Kübler, Markus Haass
Journal: Circulation (2001)

Background —In congestive heart failure (CHF), the prognostic significance of impaired respiratory muscle strength has not been established. Methods and Results —Maximal inspiratory pressure (Pi max ) was prospectively determined in 244 consecutive patients (207 men) with CHF (ischemic, n=75; idiopathic dilated cardiomyopathy, n=169; age, 54±11 years; left ventricular ejection fraction [LVEF], 22±10%). Pi max was lower in the 244 patients with CHF than in 25 control subjects (7.6±3.3 versus 10.5±3.7 kPa; P =0.001). The 57 patients (23%) who died during follow-up (23±16 months; range, 1 to 48 months) had an even more reduced Pi max (6.3±3.2 versus 8.1±3.2 kPa in survivors; P =0.001). Kaplan-Meier survival curves differentiated between patients subdivided according to quartiles for Pi max ( P =0.014). Pi max was a strong risk predictor in both univariate ( P =0.001) and multivariate Cox proportional hazard analyses ( P =0.03); multivariate analyses also included NYHA functional class, LVEF, peak oxygen consumption (peak V̇ o 2 ), and norepinephrine plasma concentration. The areas under the receiver-operating characteristic curves for prediction of 1-year survival were comparable for Pi max and peak V̇ o 2 (area under the curve [AUC], 0.68 versus 0.73; P =0.28), and they improved with the triple combination of Pi max , peak V̇ o 2 , and LVEF (AUC, 0.82; P =0.004 compared with AUC of Pi max ). Conclusions —In patients with CHF, inspiratory muscle strength is reduced and emerges as a novel, independent predictor of prognosis. Because testing for Pi max is simple in clinical practice, it might serve as an additional factor to improve risk stratification and patient selection for cardiac transplantation.