tbuckley/cabot-search huggingface dataset:
Use of lymph node ratio improves staging and selection criteria for adjuvant therapy of gastric cancer
Authors: N. G. Coburn, C. J. Swallow, A. Kiss, C. Law
Journal: Journal of Clinical Oncology (2006)

4051 Background: Despite 1997 American Joint Commission on Cancer (AJCC) guidelines stipulating assessment of ≥15 lymph nodes (LN) for staging of gastric cancer, only one third of patients in the Surveillance, Epidemiology and End Results (SEER) database from 1998–2002 had ≥15 LN assessed (ASCO 2005 #4004), with resultant understaging and probable under-treatment. In series from Asia and Europe, Lymph Node Ratio (LNR), the ratio of positive to total LN assessed, has been shown to be more accurate for staging than number of positive LN. However, most of these excluded cases with &lt;15 LN assessed. We examined the utility of LNR in a North American population. Methods: Using SEER data, we identified 9503 M0 resected gastric cancer cases from 1988–2002. LNR was categorized as 0%, 1–10%, 11–30%, 31–50% and &gt;50%. For node negative cases (LNR = 0%, n = 3652), we stratified by number of LN assessed (A=1–4; B = 5–9; C = 10–14; D≥15). For each AJCC stage or LNR strata, the degree of understaging in patients with inadequate LN assessment was measured by survival difference on Kaplan-Meier curves. Cox proportional hazard ratio (HR) models determined the effect of stratifying node negative patients and the accuracy of LNR for prognostication. Results: 27% of patients had a LNR &gt; 50%, a high proportion compared to Asian series. Fewer nodes assessed resulted in a higher likelihood of being node negative. In node negative cases, the HR of death increased for those with fewer LN assessed (vs. Group D, with 95% CI): A: HR=1.6 (1.5–1.8); B: HR = 1.3 (1.1–1.5); C: HR = 1.3 (1.1–1.5). Understaging was observed for patients with inadequate LN assessment when AJCC criteria were used (p &lt; 0.0001); this effect significantly decreased by using LNR. LNR had superior prognostic accuracy in Cox models. Conclusions: This study examines LNR in the largest series of resected gastric cancer in the literature, and the only one in which the majority of cases were inadequately staged. LNR significantly decreases understaging and improves prognostic ability. Node negative patients, nearly one third of cases, should be risk stratified by number of LN assessed, and considered for adjuvant therapy on this basis. LNR should be used to stratify node positive patients in clinical trials, and to provide more accurate staging and prognostication. No significant financial relationships to disclose.
Baseline characteristics determine long-term outcome to CRT, intermediate endpoints identify those at risk of adverse events.
Authors: A. M. W. Antonius Martinus Wilhelmus Van Stipdonk, M. Ghossein, M. Kloosterman, I. A. H. Ter Horst, F. W. Prinzen, M. Meine, K. Vernooy, A. H. Maass
Journal: European Journal of Heart Failure (2019)
Influence of Biological Parameters Assessed in [18F]FDG PET/CT on Overall Survival in Cervical Cancer Patients
Authors: Paulina Cegla, Ewa Burchardt, Andrzej Roszak, Rafal Czepczynski, Anna Kubiak, Witold Cholewinski
Journal: Clinical Nuclear Medicine (2019)

Aim The aim of this study was to estimate the influence of biological parameters assessed in [ 18 F]FDG PET/CT on overall survival (OS) in cervical cancer patients. Methods Retrospective analysis was performed on a group of 371 patients with newly diagnosed and histologically confirmed cervical cancer. PET biological parameters in primary tumor including SUV max , SUV mean , total lesion glycolysis (TLG), metabolic tumor volume (MTV), heterogeneity, and parameters referring both to primary tumor and metastatic lesions: SUV total , TLG total , and MTV total , were analyzed. Results Based on PET/CT results, 3 subgroups were identified: cervical only—with disease limited only to the cervix (38%), +regional nodes—where increased glucose accumulation in addition to the cervical area was also observed in regional lymph nodes (36%), and +distal metastases—where PET scan showed a disseminated disease (26%). Depending on the stage of the disease, in the cervical-only group, 5-year survival rate was 86%; in the +regional nodes group, it was 80%; whereas in the +distal metastases group, 5-year survival rate was only 55%. However, based on Cox regression model, significant influence on OS was found only in heterogeneity of primary tumor; more inhomogeneous tumors suggest worse prognosis (0.25 ± 0.04 vs 0.16 ± 0.09, P &lt; 0.001), SUV total (76.6 ± 130.1 vs 45.4 ± 73.4, P = 0.002), and MTV total (79.03 ± 88.27 vs 63.00 ± 83.80 cm 3 , P = 0.03). For heterogeneity, cutoff point suggesting worse prognosis was 0.18; for SUV total , 52.3; and for MTV total , 66.55 cm 3 . Conclusions Stage of disease assessed in [ 18 F]FDG PET/CT significantly influences survival rate in patients with cervical cancer. SUV total , MTV total , and heterogeneity of primary tumor are independent prognostic factors on OS in cervical cancer patients.
Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study
Authors: Gabriele Valentini, Dörte Huscher, Antonella Riccardi, Serena Fasano, Rosaria Irace, Valentina Messiniti, Marco Matucci-Cerinic, Serena Guiducci, Oliver Distler, Britta Maurer, Jérôme Avouac, Ingo H Tarner, Marc Frerix, Gabriela Riemekasten, Elise Siegert, László Czirják, Veronika Lóránd, Christopher P Denton, Svetlana Nihtyanova, Ulrich A Walker, Veronika K Jaeger, Francesco Del Galdo, Giuseppina Abignano, Lidia P Ananieva, Ana Maria Gherghe, Carina Mihai, Joerg Christoph Henes, Tim Schmeiser, Alessandra Vacca, Sergey Moiseev, Ivan Foeldvari, Armando Gabrielli, Brigitte Krummel-Lorenz, Simona Rednic, Yannick Allanore, Ulf Müeller-Ladner
Journal: Annals of the Rheumatic Diseases (2019)

To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc).601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05).The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.
Cardiac Problems in Pregnancy
Authors: Uri Elkayam
Journal: JAMA (1984)

RAPID progress in the field of cardiology during the past decade has resulted in the development of new technology and its application to more sophisticated diagnosis and therapy. This development has led to vast improvements in the medical care available to all cardiac patients, including pregnant women. These developments, it seems, should have made it possible now for most cardiac patients to carry a pregnancy to a successful outcome. The purpose of this article is therefore to assess the recommended current approach to treatment of the pregnant patient with heart disease in view of recent progress in cardiovascular medicine. The approach to medical care in the cardiac patient has gone through a significant liberalization process over the years. While the early literature viewed pregnancy as contraindicated for all patients with valvular heart disease,<sup>1</sup>later reports suggested that therapeutic abortions are rarely indicated for patients with heart disease.<sup>2</sup>In
Efficacy and safety of methotrexate versus placebo as add-on therapy to H1 antihistamines for patients with difficult-to-treat chronic spontaneous urticaria: A randomized, controlled trial
Authors: Sophie Leducq, Mahtab Samimi, Claire Bernier, Angèle Soria, Emmanuelle Amsler, Delphine Staumont-Sallé, Germaine Gabison, Olivier Chosidow, Nathalie Bénéton, Corina Bara, Anne Grange-Prunier, Ewa Wierzbicka-Hainaut, Emilie Brenaut, Catherine Droitcourt, Nathalie Raison-Peyron, Hélène Bourgoin, Hélène Cornillier, Laurent Machet, Bruno Giraudeau, Agnès Caille, Annabel Maruani
Journal: Journal of the American Academy of Dermatology (2019)
The effects of gemcitabine on cell apoptosis and cycle of gastric cancer
Authors: L. Wang
Journal: Journal of Clinical Oncology (2007)

15181 Background: To study the effects of gemcitabine on cell apoptosis and cell cycle of gastric cancer Methods: Gastric cancer cells were cultured with different concentrations of gemcitabine (0.001, 0.01 and 0.1μM). MTT test was performed to evaluate the cell proliferation. The cells were divided into three groups: control group (cultured in RPMI-1640) and 5-FU group ( cultured in RPMI-1640 with 5- FU) and gemcitabine group ( cultured in RPMI-1640 with Gemcitabine). Flow cytometry was performed to determine the apoptotic rate and the cell cycle phases. Morphological changes were observed by phasecontrast microscope. Results: The cell proliferation was inhibited in experiment groups treated with gemcitabine and 5-FU, compared with control groups(P&lt;0.01). Gemcitabine can induce cell apoptosis. 0.01μM and 0.1μM gemcitabine were much more effective than 0.001μM. On the third day, S phase cells accounted for 24.5% and G 2 -M phase cells 0.08% in the control group, while 24.6% and 0.06%, respectively in the gemcitabine group. However, on the seventh day, those came to 20.8% and 0.41% in the control group, and 18.2% and 1. 55% in the gemcitabine group, indicating a significant change in the cell cycle ( P&lt;0.01). Conclusions: Gemcitabine can inhibit the cell proliferation, and it maybe related to cell apoptosis. No significant financial relationships to disclose.
Zebrafish oxytocin neurons drive nocifensive behavior via brainstem premotor targets
Authors: Caroline L. Wee, Maxim Nikitchenko, Wei-Chun Wang, Sasha J. Luks-Morgan, Erin Song, James A. Gagnon, Owen Randlett, Isaac H. Bianco, Alix M. B. Lacoste, Elena Glushenkova, Joshua P. Barrios, Alexander F. Schier, Samuel Kunes, Florian Engert, Adam D. Douglass
Journal: Nature Neuroscience (2019)
Parenteral L-Arginine Improves Mitochondrial Function in Children with Sickle Cell Disease Admitted for Vaso-Occlusive Pain Episodes
Authors: Sruti Shiva, Lou Ann Brown, Y Wang, Carlton Dampier, Amanda Watt, Vinita Tripathi, Amina Bhutta, Polly Kumari, Janet Figueroa, April Zmitrovich, Claudia R. Morris
Journal: Blood (2018)
ER, PR, and HER2 assessment in Hispanic women with breast cancer: A comparison between IHC and AQUA technology.
Authors: Anna Maria Di Marco, Jose Alberto Ruiz, Maryangely Moreno, Carlos El Hader, Luis Baez
Journal: Journal of Clinical Oncology (2013)

e11568 Background: Estrogen (ER), progesterone (PR) receptors and HER2 are important markers for breast cancer (BC) treatment planning. These markers are often measured by immunochemistry (IHC) but IHC is subject to limitations of operator subjectivity and equivocal results making selection of appropriate therapy difficult and ultimately affecting patient outcome. Methods: 135 females with BC were recruited in Puerto Rico between Sept and Dec 2012. Median patient age was 57 and 95 % had invasive ductal carcinoma. Our aim was to compare discordance rates of ER, PR and HER2 between IHC and AQUA, an automated fluorescent technology that quantifies antigen expression, in a population of Hispanic women and to investigate whether specimen type or tumor grade influence discordance rate between the two technologies. Results: 103 of 135 patient samples were found to be ER+ by both technologies and 28 samples were ER- by both IHC and AQUA. 4 samples (3%) were discordant; 2 each were AQUA+/IHC- and AQUA-/IHC+. 73 of 135 samples expressed PR by both technologies and 55 samples were PR- by both IHC and AQUA. 14 samples (10%) were discordant; 7 each were AQUA+/IHC- and AQUA-/IHC+. 87 of 135 samples were HER2- and 13 patients were found to be HER2+ by both technologies. However 35 samples (26%) were discordant for HER2 status; 31 were AQUA+/IHC- while 4 AQUA-/IHC+. 100 of the HER2 results were scored 0-1 (negative) by IHC and 25 % of these cases were overturned by AQUA to HER2 +. 19 of the HER2 results were scored 2 (borderline) by IHC. 32 % of these cases were positive by AQUA. Conclusions: Discordance rate were 3% for ER, 10 % for PR but 26% for HER2 between IHC and AQUA. The Cohen’s Kappa coefficient for ER and PR were 0.914 and 0.785 respectively but only 0.299 for HER2 (p values &lt; 0.00001 for all 3 values). Needle/core biopsy yielded more HER2 discordance than lumpectomy/mastectomy (31% vs. 16%). HER2 discordance between IHC and AQUA was more common in higher grade tumors. The large number of HER2 negative IHC cases scored positive by AQUA, and considering the data demonstrating that HER2 by AQUA better predicts benefit from trastuzumab (Slamon D, SABCS 2012) suggests that a significant additional number of patients could benefit from such targeted therapy.
The role of AP-1 in colon cancer stem cells.
Authors: Marina Chatziioannou, Panagiotis Apostolou, Maria Toloudi, Eleni Ioannou, Asir Kopic, Dimitrios Komiotis, Ioannis Papasotiriou
Journal: Journal of Clinical Oncology (2013)

e14699 Background: The AP-1 transcription factor is a heterodimeric protein, which regulates gene expression in response to a variety of stimuli. The above factor also regulates cellular processes including differentiation, proliferation and apoptosis. The AP-1 heterodimeric protein is consisted of the combination of c-Jun and c-Fos proteins. The c-Jun is activated through phosphorylation, but it has also phosphorylation independent function. The c-FOS is a cellular proto-oncogene, which is up-regulated in response to many extracellular signals. The present study aim to find out the effect of c-FOS gene in Colon CSCs according to stemness. Methods: In all experiments there have been used established human colon cancer stem cells (CelProgen). Experiments for suppression of c-FOS expression, by using specific siRNA were performed and the transfection was evaluated with qPCR assays. The stemness transcription factors Nanog, Oct3/4 and Sox2 were tested with gene expression assays, and a relative quantification was performed according to Livak method. The CD44 and CD26 genes were used as positive markers in colon cancer in all procedures. Results: The results indicated that the c-FOS proto-oncogene affects the gene expression of transcription factors, which are essential for the maintenance of stemness. However the results were different, depending on the rate of suppression. The suppression of c-FOS by 65% led to increase in gene expression of stemness transcription factors, with higher rates for Nanog, smaller for Sox2 and minimum for Oct3/4. Unlike results were observed when the expression was suppressed by 85%. In this case there was observed higher decrease in Oct3/4 and less in the other markers. Conclusions: Up to now studies have demonstrated the significant role of c-JUN in stem cells, but little is known about the other half of AP-1 complex, the c-FOS gene. In the first part of the study it was confirmed the effect of c-FOS in stemness, as it was observed change in gene expression of stemness’s significant transcription factors. However it is indicated that there is a cross-talk between JNK pathway and stemness. Further studies in more samples are needed to demonstrate all the above, so that it can be used at clinical level.
Efficacy and safety of sorafenib in patients with advanced clear-cell renal cell carcinoma (RCC) with diabetes: Results from the phase III TARGET study
Authors: S. Oudard, T. Eisen, C. Szczylik, M. Siebels, S. Negrier, C. Chevreau, F. Cihon, R. M. Bukowski, B. Escudier
Journal: Journal of Clinical Oncology (2009)

e16099 Background: Results of the phase III TARGET trial, a randomized, double-blind, placebo-controlled study of sorafenib (SOR) treatment in pts with clear-cell RCC in whom 1 prior systemic therapy had failed, indicated that SOR is effective and safe for pts with advanced RCC, leading to the approval of SOR for the treatment of advanced RCC. Diabetes can be associated with increased morbidity during treatment in a variety of malignancies. Therefore, an exploratory subset analysis was performed to evaluate the efficacy and safety of SOR in pts enrolled in TARGET with or without diabetes at baseline. Methods: Pts (N=903) with advanced clear-cell RCC, ECOG PS 0–2, and low- or intermediate-risk MSKCC score were randomized 1:1 to SOR 400 mg BID or placebo (PBO). End points included OS, PFS, and safety. A planned independently-assessed formal analysis of PFS showed significant benefit for SOR over PBO; consequently, pts assigned to PBO were able to cross over to SOR. Results: Pt demographics were similar for all subsets. Pre- crossover data by subset are shown in the table . The incidence of drug-related adverse events (AEs) across subgroups was consistent with that for the overall population. In pts with vs without diabetes, treatment with SOR was not associated with increased hyperglycemia (1 pt/arm in the without diabetes subgroups only) or hypertension. Conclusions: The safety profile of SOR in pts with diabetes was comparable with that for the overall study population. SOR was well tolerated and AEs were manageable. Trends in improved PFS were observed for SOR regardless of baseline diabetes status; however, the small diabetic subset limits interpretation of a SOR OS benefit in this subpopulation. *Final PFS of overall study population based on independent review from Jan 2005; all other data from May 2005 database [Table: see text] [Table: see text]
Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors
Authors: Elizabeth M. Cespedes Feliciano, Wendy Y. Chen, Patrick T. Bradshaw, Carla M. Prado, Stacey Alexeeff, Kathleen B. Albers, Adrienne L. Castillo, Bette J. Caan
Journal: Journal of Clinical Oncology (2019)

PURPOSE Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer. METHODS Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors. RESULTS Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]). CONCLUSION Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.
Effect of 13q deletion on IL-6 production in patients with multiple myeloma.
Authors: Hamdy A. Azim, Neemat Kassem, Rania H Khalifa, Tarek Yakout Mohamed
Journal: Journal of Clinical Oncology (2012)

e18570 Background: Numerous studies have shown a correlation between 13q deletion and poor prognosis in multiple myeloma (MM), but the mechanisms are not fully understood. Earlier studies suggest that this lesion involves large segments or the entire long arm involving the retinoblastoma (Rb) gene. In myeloma, Rb gene is believed to down regulate interleukin -6 (IL-6) which plays a central role in the pathogenesis of MM. Therefore, it has been hypothesized that loss of Rb gene might be associated with very high expression of IL-6 and subsequent bad prognosis. Methods: Forty MM patients and 20 matched controls were included in this study. Interphase fluorescence in situ hybridization (FISH) analysis was performed using LSI 13q14-specific probe. Serum levels of IL-6 were determined by ELISA. All patients received conventional chemotherapy. Refractory patients received other therapeutic regimen of thalidomide or bortezomib. Results: Significant increase (p &lt; 0.001) of IL-6 production was recorded in patients with 13q deletion compared to patients with normal chromosome 13q status. These patients were also refractory to conventional chemotherapy but showed striking response to thalidomide or bortezomib. Conclusions: This study suggests that 13q deletions are associated with increased production of IL-6 in MM and this could be a possible cause of the associated bad prognosis. In addition, the results also show the potential to improve responses inpatients with refractory MM with the introduction of novel therapies.