tbuckley/cabot-search huggingface dataset:
A phase II study evaluating the role of sentinel lymph node surgery and axillary lymph node dissection following preoperative chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis: ACOSOG Z1071.
Authors: K. Hunt, H. T. Le-Petross, V. Suman, B. G. Haffty, A. M. Leitch, D. Ollila, D. R. Byrd, T. A. Buchholz, W. F. Symmans, J. C. Boughey
Journal: Journal of Clinical Oncology (2010)

TPS118 Background: In patients presenting with lymph node positive breast cancer who undergo preoperative chemotherapy the standard of care is completion axillary lymph node dissection (ALND) at the time of surgical resection. The goal of this phase II single-arm study is to evaluate the false-negative rate (FNR) of sentinel lymph node (SLN) surgery after completion of neoadjuvant chemotherapy in patients who initially presented with node-positive disease. If results of this study show that SLN surgery has an acceptable FNR for staging of the axilla after preoperative chemotherapy in patients who initially had node-positive disease, this would change the surgical standard of care for these patients and patients with negative SLNs could be spared the morbidity of complete ALND, significantly reducing the short-term and long-term surgical morbidity associated with the treatment of node-positive breast cancer. Methods: Single-arm study activated in July 2009 with a target accrual of 550 patients. The primary objective is to determine the false- negative rate (FNR) for SLN surgery. FNR is defined as the number of patients declared to have no evidence of cancer in the SLN and are found to have at least one positive lymph node in the ALND divided by the total number of patients with at least one positive axillary lymph node by ALND. Eligible patients are adult women with biopsy-proven invasive breast cancer and biopsy of an axillary lymph node documenting nodal disease prior to initiation of preoperative chemotherapy. Patients with prior ipsilateral axillary surgery or SLN surgery are not eligible. Imaging correlatives will determine how the axillary ultrasound status of the patient upon completion of preoperative chemotherapy (evidence of residual lymphadenopathy on ultrasound versus no evidence of lymphadenopathy) affects the FNR of SLN surgery and how sonographic findings correlate with residual disease on final pathology. Additional correlative science studies will examine the incidence, risk factors, and changes in quality of life associated with the development of lymphedema following ALND. No significant financial relationships to disclose.
Abstract 1978: Patterns of Late Gadolinium Enhancement are Associated with Ventricular Stiffness in Patients with Advanced Non-Ischemic Dilated Cardiomyopathy
Authors: Eui-Young Choi, Sung-Ai Kim, Chi-Young Shim, Se-Jung Yoon, Byoung Ho Lee, Byoung Wook Choi, Jong-Won Ha, Se-Joong Rim, Namsik Chung
Journal: Circulation (2007)

Background: In patients with advanced systolic heart failure, restriction of left ventricular (LV) filling or mechanical dyssynchrony rather than lower ejection fraction (EF) is more associated with poor prognosis. However, structural determinants of these parameters have not been fully studied. Objectives: We investigated whether patterns of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) affect the ventricular mechanics and fillings in patients with non-ischemic dilated cardiomyopathy (DCM). Methods: Patients with markedly reduced systolic function (LVEF &lt;35%) due to longstanding (&gt; 6 months) non-ischemic DCM underwent CMR after comprehensive echo-Doppler evaluations. Intraventricular synchrony index was measured by standard deviation of time to peak longitudinal contractions (Ts-SD) in 12 LV segments. Patients with significant aortic regurgitation or atrial fibrillation were excluded. Results: Patients (n=49) could be divided into three groups according to LGE patterns as non-LGE group (n=18), non-midwall LGE group (n=13) and midwall LGE group (n=18). There were no differences in clinical characteristics, LV dimension, LVEF and Ts-SD among three groups. However, in terms of LV longitudinal mechanics, midwall LGE group was associated with higher E/Em and lower Am and Sm. Moreover, diastolic LV stiffness index (Ed), defined as E/Em/stroke volume (ml), was significantly higher in midwall LGE group compared with non-LGE group (0.85±0.51 vs. 0.41±0.21, p=0.002), and non-midwall LGE group (0.85±0.51 vs. 0.46±0.31, p=0.008). Conclusions: Presence and patterns of LGE is associated with ventricular filling and stiffness in advanced non-ischemic dilated cardiomyopathy.
Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study.
Authors: M J Borowitz, J J Shuster, C I Civin, A J Carroll, A T Look, F G Behm, V J Land, D J Pullen, W M Crist
Journal: Journal of Clinical Oncology (1990)

We studied the blasts from 795 children greater than 1 year of age with newly diagnosed, untreated B-precursor acute lymphoblastic leukemia (ALL) for expression of the hematopoietic stem cell-associated antigen CD34. All cases were confirmed as B-lineage lymphoblastic leukemia by virtue of expression of CD19 and/or CD22, lack of T-cell antigens, and lack of surface-membrane immunoglobulin (Ig). The CD34 antigen was present in at least 10% of blast cells in 587 (73.8%) of the patients. There was no significant difference in presenting clinical characteristics between CD34+ and CD34- patients save for an increased incidence of CNS involvement at diagnosis in the latter. Patients with CD34+ leukemia were more likely to have blasts expressing CD22, CD9, and CD13 antigens but were less likely to coexpress CD20. Patients with pre-B (cytoplasmic mu) ALL were significantly more likely to lack CD34 on their blasts, while children with hyperdiploid ALL were more likely to be CD34+. Although remission induction rates were not significantly different between patients with CD34+ and CD34-ALL (P = .23), event-free survival was shorter for patients with CD34- leukemia (P = .0014). Even though CD34 expression was associated with certain other known prognostically favorable variables including hyperdiploidy and lack of cytoplasmic Ig, it had an independent favorable effect on treatment outcome, even after adjusting for competing prognostic factors.
Molecular and Genomic Impact of Large and Small Lateral Dimension Graphene Oxide Sheets on Human Immune Cells from Healthy Donors
Authors: Marco Orecchioni, Dhifaf A. Jasim, Mario Pescatori, Roberto Manetti, Claudio Fozza, Francesco Sgarrella, Davide Bedognetti, Alberto Bianco, Kostas Kostarelos, Lucia Gemma Delogu
Journal: Advanced Healthcare Materials (2015)

Graphene oxide (GO) is attracting great interest in biomedical sciences. The impact of GO on immune cells is one fundamental area of study that is often overlooked, but critical in terms of clinical translation. This work investigates the effects of two types of thoroughly characterized GO sheets, different in their lateral dimension, on human peripheral immune cells provided from healthy donors using a wide range of assays. After evaluation of cell viability, the gene expression was analyzed, following GO exposure on 84 genes related to innate and adaptive immune responses. Exposure to GO small sheets was found to have a more significant impact on immune cells compared to GO large sheets, reflected in the upregulation of critical genes implicated in immune responses and the release of cytokines IL1β and TNFα. These findings were further confirmed by whole‐genome microarray analysis of the impact of small GO sheets on T cells and monocytes. Activation in both cell types was underlined by the overexpression of genes such as CXCL10 and receptor CXCR3. Significant energy‐dependent pathway modulation was identified. These findings can potentially pave the foundations for further design of graphene that can be used for immune modulation applications, for example in cancer immunotherapy.
Irritable bowel syndrome: new and emerging treatments
Authors: M. Halland, Y. A. Saito
Journal: BMJ (2015)

Irritable bowel syndrome is one of the most common gastrointestinal disorders in developed nations. It is characterized by abdominal pain, altered bowel habits, and bloating. Several non-pharmacological and pharmacological agents, which target the peripheral gastrointestinal system and central nervous system, are used to treat the syndrome. The individual and societal impact of investigating and managing the syndrome is substantial, and despite newer treatments, many patients have unmet needs. Intense research at many international sites has improved the understanding of pathophysiology of the syndrome, but developing treatments that are effective, safe, and that have tolerable side effects remains a challenge. This review briefly summarizes the currently available treatments for irritable bowel syndrome then focuses on newer non-pharmacological and pharmacological therapies and recent evidence for older treatments. Recent guidelines on the treatment of irritable bowel syndrome are also discussed.
Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease
Authors: Christian Lood, Luz P Blanco, Monica M Purmalek, Carmelo Carmona-Rivera, Suk S De Ravin, Carolyne K Smith, Harry L Malech, Jeffrey A Ledbetter, Keith B Elkon, Mariana J Kaplan
Journal: Nature Medicine (2016)
Cognitive disfunctions in women with breast cancer treated with adjuvant chemotherapy: A preliminary report
Authors: D. Gercovich, H. Hirsch, P. Lopez, N. Gercovich, L. Vázquez, E. Gil Deza, G. Martin Reina, P. Margiolakis, E. Morgenfeld, F. G. Gercovich
Journal: Journal of Clinical Oncology (2009)

e20742 Background: Recent studies suggest that women diagnosed with breast cancer and treated with adjuvant chemotherapy may suffer cognitive deterioration. These studies, however, present a number of limitations including a small sample of patients, retrospective evaluation of cognitive skills, lack of cognitive-function measurements previous to the chemotherapy and a lack of evaluation of psycho-pathological factors that could potentially influence on the cognitive function of the subjects. The aim of this study is to present the preliminary results of a prospective study about the impact of conventional adjuvant chemotherapy on a series of cognitive domains in adult women diagnosed with breast carcinoma, monitoring frequent psycho-pathological variables such as anxiety and depression. Methods: The present is a cohort, observational study. It includes patients with a diagnosis of stage I and II breast carcinoma, treated with standard chemotherapy and able to give their consent. The protocol has 3 stages of evaluation. First evaluation: a basal measurement between diagnosis and the first chemotherapy course. The second and third evaluations are done at 8 and 14 months respectively after the first one. Each patient has been studied using a neuro-psychological battery of 17 different tests which evaluate the following cognitive domains: global cognitive functioning, intelligence, memory, language and executive functions. The levels of anxiety and depression were studied simultaneously. Further tests will be done for related samples, so as to compare changes within a group. Results: Up to date 14, patients have completed the basal battery of tests. We expect to find differences in the cognitive functions of the patients treated with adjuvant chemotherapy. The aforementioned differences will be controlled with psycho-pathological measurements. Conclusions: The present study will allow us to evaluate in a prospective and exhaustive way cognitive deficiencies in women with breast carcinoma treated with adjuvant chemotherapy. In addition, the use of psycho-pathological instruments will allow monitoring and understanding the neuro-psychological results in a more reliable way. No significant financial relationships to disclose.
Low-dose aminoglutethimide with and without hydrocortisone replacement as a first-line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.
Authors: G Cocconi, G Bisagni, G Ceci, M Bacchi, C Boni, M Brugia, A Carpi, F Di Costanzo, V Franciosi, S Gori
Journal: Journal of Clinical Oncology (1992)

PURPOSE A randomized study comparing low-dose aminoglutethimide (AG) with and without hydrocortisone (HC) was performed to investigate whether corticosteroid replacement contributes to the therapeutic effects of the drug administered as a front-line endocrine therapy in postmenopausal advanced breast cancer. PATIENTS AND METHODS Postmenopausal patients who had not had prior endocrine therapy for advanced disease and with estrogen receptor (ER) or progesterone receptor (PgR) status positive or unknown were eligible. AG was administered at a dose of 250 mg twice a day orally (125 mg twice a day during the first month) with or without HC (20 mg twice a day orally). Seventy-nine and 74 patients were assessable for response on the AG plus HC arm and on the AG arm, respectively. The two treatment groups were well balanced and patients were largely untreated. Approximately 60% had not received any adjuvant treatment, and approximately 75% had not received any medical treatment after relapse. RESULTS The overall responses (complete response [CR] plus partial response [PR]) were 44% and 41% for the AG plus HC and the AG arm, respectively, showing no significant difference. Time to progression (median, 8.1 and 6.3 months), duration of response (median, 15.8 and 13.7 months), and duration of survival (median, 34.2 and 36.3 months) were not significantly different between the two treatment arms. Side effects were infrequent and mild in both arms, with no significant differences. CONCLUSION We conclude that half of the conventional daily dose of AG has optimal therapeutic activity as a front-line endocrine treatment of postmenopausal advanced breast cancer and that HC does not significantly contribute to the therapeutic effects.
Chemoprotection by VEGF: Rationale for combination nab-paclitaxel and bevacizumab
Authors: V. Trieu, S. Ran, C. Bivens, N. Desai
Journal: Journal of Clinical Oncology (2007)

1064 Background: Nanoparticle albumin-bound (nab-) paclitaxel (ABX) has shown greater efficacy and less toxicity than solvent-based paclitaxel (TAX) in xenograft models and clinical trials. The goal of this study was to determine the effects of VEGF modulation in human MDA-MB-231 breast tumor cell line and the effects of ABX and VEGF-neutralizing antibody bevacizumab (AVA) combination on the growth and metastasis of orthotopically implanted MDA-MB-231 tumors. Methods: VEGF expression was evaluated by ELISA in MDA-MB-231 tumor extract one week after treatment (qdx5) with saline, doxorubicin (10 mg/kg), TAX (10 mg/kg), or ABX (15 mg/kg). VEGF-receptor expression in MDA-MB-231 was quantitated by RT-PCR. MDA-MB-231 cytotoxicity with ABX, VEGF, AVA alone or in combination was measured by cytotoxicity and clonogenic assays. Implanted MDA-MB-231 tumors expressing luciferase were treated with saline, 2 cycles of ABX (10 mg/kg, two qdx5 cycles separated by 1 week, N=5) alone or in combination with AVA (2, 4 and 8 mg/kg, 2/wkx6). Tumor lymph node and pulmonary metastasis was determined by measuring luciferase activity. Results: Compared with saline, MDA-MB-231 tumors following chemotherapies exhibited significant tumor shrinkage (p≤0.006, t-test) and VEGF induction (p&lt;0.0001, t-test). MDA-MB-231 was shown to express VEGFR2. Exogenous VEGF had a protective effect on MDA-MB-231 tumor cells by reducing cytotoxicity of ABX in both cytotoxicity and clonogenic assays. Sequestration of VEGF with AVA increased cytotoxicity of ABX in vitro. Treatment of MDA-MB-231 breast tumors with ABX and AVA combination resulted in greater than additive antitumor response and significantly reduced metastasis to the lungs (p=0.025 vs control) and LN (p=0.022) at the highest AVA dose. Conclusions: Chemotherapies induced VEGF expression in MDA-MD-231 breast tumor in vivo. In vitro, VEGF exerted a protective effect against ABX chemotherapy in VEGFR2-expressing MDA-MD-231 cells, which was abrogated by addition of AVA. In vivo, ABX and AVA combination significantly inhibited the metastatic potential of MDA-MB-231 tumor cells. These data provide a rational basis for the combination of nab- paclitaxel and bevacizumab in VEGF-receptor expressing tumors. [Table: see text]
Commentary on ""
Authors: Tim Wood
Journal: British Journal of Sports Medicine (2007)

<h3>Objective</h3> Although a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their mechanisms in GC development. <h3>Design</h3> We conducted a meta-analysis of four genome-wide association studies (GWASs) encompassing 3771 cases and 5426 controls. After targeted sequencing and functional annotation, we performed in vitro and in vivo experiments to confirm the functions of genetic variants and candidate genes. Moreover, we selected 33 promising variants for two-stage replication in 7035 cases and 8323 controls from other five studies. <h3>Results</h3> The meta-analysis of GWASs identified three loci at 1q22, 5p13.1 and 10q23.33 associated with GC risk at p&lt;5×10<sup>−</sup><sup>8</sup> and replicated seven known loci at p&lt;0.05. At 5p13.1, the risk rs59133000[C] allele enhanced the binding affinity of NF-κB1 (nuclear factor kappa B subunit 1) to the promoter of <i>PRKAA1</i>, resulting in a reduced promoter activity and lower expression. The knockout of <i>PRKAA1</i> promoted both GC cell proliferation and xenograft tumour growth in nude mice. At 10q23.33, the rs3781266[C] and rs3740365[T] risk alleles in complete linkage disequilibrium disrupted and created, respectively, the binding motifs of POU2F1 and PAX3, resulting in an increased enhancer activity and expression of <i>NOC3L</i>, while the <i>NOC3L</i> knockdown suppressed GC cell growth. Moreover, two new loci at 3q11.2 (OR=1.21, p=4.56×10<sup>−</sup><sup>9</sup>) and 4q28.1 (OR=1.14, p=3.33×10<sup>−</sup><sup>11</sup>) were associated with GC risk. <h3>Conclusion</h3> We identified 12 loci to be associated with GC risk in Chinese populations and deciphered the mechanisms of <i>PRKAA1</i> at 5p13.1 and <i>NOC3L</i> at 10q23.33 in gastric tumourigenesis.
Metabolic syndrome in patients with COPD
Authors: Renata Rubinsztajn, Tadeusz Przybylowski, Marta Maskey-Warzechowska, Magdalena Paplinska-Goryca, Patrycja Nejman-Gryz, Krzysztof Karwat, Ryszarda Chazan
Journal: European Respiratory Journal (2014)

COPD is a systemic disease which may be associated with various pathologies including metabolic disorders.

The aim of the study was to estimate the frequency the metabolic syndrome (MS) in COPD patients.

Material and methods : MS was diagnosed in accordance with the recommendations of the Polish Forum of Cardiovascular Disease Prevention. The study group consisted of 275 patients (173M, 102F) with stable COPD in all stages of severity All patients underwent spirometry, body composition was analyzed by bioimpendance. The following blood tests were evaluated: CRP, IL-6, leptin, adiponectin, endothelin using ELISA R&D system

Results

MS was diagnosed in 96 patients (34.5%). No differences were observed in the frequency of MS in different stages of COPD severity (GOLD 2010 stage I-IV: 42.9; 35.9; 32.2; 34%, respectively). FEV1 (% predicted), FVC (% predicted), 6MWD, age and the number of pack-years was similar in both groups. MS was more frequent in males (38.7 vs. 28.4%). Patients with MS had a higher systolic blood pressure: 126mmHg (120 -140) vs.118 mmHg (110-130). There were significant differences in body composition between the MS+ and MS- ( Fat mass index: 9.4vs7.8 kg/m2; Fat free mass index 19.1vs18 kg/m2; Muscle mass index 18.4 vs 17.2kg/m2; Total body water 40 vs 35.4kg; Basic energy rate1603 vs 1423 kcal.) and blood tests ( IL-6 4.7 vs 2.7 pg/ml; endothelin 1.9 vs 1.8 mg/l; leptine 14.5 vs 10.7µ/l; adiponectine 6.7 vs 10.9mg/l; CRP 4.6 vs 2.5 mg/l)

Conclusions

MS may be a comorbidity all COPD stages and its frequency does not depend on COPD severity. The activity of systemic inflammation is higher in MS+ patients, so MS can affect the natural history of COPD and should be considered in the routine evaluation of patients with disease.
Triple-negative metastatic/recurrent breast cancer: Treatment with paclitaxel/carboplatin combination chemotherapy
Authors: J. W. Chia, P. Ang, H. See, Z. Wong, L. Soh, Y. Yap, N. Wong
Journal: Journal of Clinical Oncology (2007)

1086 Background: Patients with triple negative (ER, PR, Her2 negative) breast cancers do not derive benefit from Herceptin or hormonal agents. For them, conventional chemotherapy remains the only option. Recent data suggests that triple negative breast cancers (TNBC) have increased sensitivity to platinum agents. We conducted a retrospective analysis to determine the response rates of such patients treated with paclitaxel and carboplatin (TC) chemotherapy. Methods: Patients with metastatic/recurrent TNBC were included in our study. Chemotherapy administered at weekly (paclitaxel 80mg/m 2 and carboplatin AUC2 on D1, D8, D15) or 3 weekly intervals (paclitaxel 175mg/m 2 and Carboplatin AUC 5 on D1). ER and PR status was defined using IHC. Her 2 positive was defined by a positive FISH or 3+ IHC staining. Results: 101 patients with TNBC were diagnosed at our centre from 2002 to 2005 and of these only 23 patients had metastatic/ recurrent disease. 14 patients were treated with TC and therefore included in our analysis. Median age of patients was 53 yrs (range 36 to 68yrs). 3 patients had metastatic disease at diagnosis and 11 patients were treated for recurrent disease. Median time to recurrence for this subgroup was 20 months (range 8 to 224mths). 4 and 6 patients had prior adjuvant exposure to taxanes and anthracyclines respectively. Median prior lines of chemotherapy was 1 (range 0–4). Median number of disease sites in patients was 4. Eight patients (57%) experience a partial response (PR) with TC. 2 patients had stable disease and 4 progressive disease. Although no patients experienced complete response, 3 patients had good PR. One patient with metastatic disease had complete resolution of a large, 9cm locally invasive breast tumor after 3 cycles of TC. The second had a 90% reduction in volume of a large chest wall recurrence after 2 cycles TC. Patients who had 2 or 3 prior lines of chemotherapy also continued to show response. The median time to tumor progression was 16 weeks (range 4–28 wks). Conclusions: TC gives a high response rate in patients with metastatic/ recurrent TNBC. Patients with prior exposure to taxanes and those with large volume disease showed good response. Randomised trials are underway to compare the TC regimen with non-platinum containing doublets. No significant financial relationships to disclose.