tbuckley/cabot-search huggingface dataset:
Polymorphisms in VEGF, eNOS, COX-2, and IL-8 as predictive markers of response to bevacizumab.
Authors: L. lo Giudice, M. Di Salvatore, A. Astone, M. Rodriquenz, G. Nazzicone, A. Cassano, C. Bagalà, C. Santonocito, E. D. Capoluongo, C. Barone
Journal: Journal of Clinical Oncology (2010)

e13502 Background: There are no validated predictive markers for selecting patients who would respond to bevacizumab. Previous studies analyzed the role of SNPs in VEGF, eNOS, COX-2, IL-8, but no definite prognostic and predictive association has been established. We evaluated the association of genetic variability with outcome in patients (pts) treated with bevacizumab. Methods: Fifty metastatic pts affected by colorectal (35/50), breast (11/50), and kidney (4/50) cancer were included in this study. VEGF936 C/T and VEGF2578 C/A, eNOS894 G/T, eNOS786 T/C, COX-2 8473 C/T, IL-8 251 T/A polymorphisms were selected. All pts were treated with bevacizumab plus chemotherapy (colorectal and breast cancer) or IFN (renal cancer). Response rate was related to polymorphic gene expression. The relationship of TTP/OS to SNPs is too early because most pts are still alive. The association between response and genotypes was evaluated using the Chi-square test. Results: 29/50 (58%) pts had a partial response, one patient had a complete response and 20 (40%) pts a stable disease. 39/50 (78%) pts were VEGF936 CC (wt) and 11 (22%) VEGF936 CT. 20/50 (40%) pts were VEGF2578 CC (wt), 19 (38%) VEGF2578 CA and 11 (22%) VEGF2578 AA. 16/50 (32%) pts were eNOS894 GG (wt), 27 (54%) eNOS894 GT and 7 (14%) eNOS894 TT. 17/50 (34%) pts were eNOS786 TT (wt), 24 (48%) eNOS786 CT, 9 (18%) eNOS786 CC. All patients were COX-2 8473 CC (wt). The SNP IL-8 251 T/A was tested only in patients with colorectal cancer (35 pts) and 20/35 resulted IL-8 251 TT (wt), 6 pts were IL-8 251 TA and 9 pts IL-8 251 AA. The eNOS786 TT genotype (wt), compared to genotype CC, was associated with a best response to treatment in breast (RR 36.4% vs 18.2%; p=0.036) and colorectal cancer (RR 28.6% vs. 8.6%; p=0.04). The IL-8 251 TT genotype (wt), was associated with a best response to bevacizumab in colorectal cancer, when compared with the genotype AA (RR 25.7% vs 14.3%; p=0.04). Conclusions: With increasing number of antiangiogenic agents, the need of biomarkers is becoming critical, either due to hight cost of these treatments and to response variability. Our preliminary results suggest that the study of SNPs of some genes involved in angiogenesis might be useful in improving the selection of potentially responsive pts. No significant financial relationships to disclose.
Breastfeeding and rhinoconjunctivitis: A cohort study
Authors: Cristian Dogaru, Anina Pescatore, Jennifer Baeuml, Ben Spycher, Erol Gaillard, Caroline Beardsmore, Claudia Kuehni
Journal: European Respiratory Journal (2013)

Aim   It is postulated that breastfeeding (BF) reduces the risk of atopic diseases including rhinoconjunctivitis (RC) in children, but the available evidence is inconclusive. We examined the association between BF and reported hayfever (HF) and symptoms of RC in a large population-based cohort   Method   We assessed BF in children aged 1-4 years from Leicestershire, UK. We sent questionnaires at age 6-10 and again at 13-18 yrs, asking about recent (past 12 months) HF, symptoms of RC (runny nose and itchy/watery eyes) and severe RC (SRC, RC affecting activity). We ran logistic regressions separately for HF, RC and SRC, adjusting for age, sex, ethnicity, smoking in pregnancy, family history of atopy, early exposure to infections, socio-economic status and early signs of atopy (wheeze or eczema)   Results   Of 6768 participants with BF data at recruitment, 4236 and 2542 responded at age 6-10 and 13-18 years. 2732 (40%) were never breastfed. From age 6-10 to 13-18 there was an increase in prevalence of HF (14% to 36%), RC (12% to 22%) and SRC (3% to 5%). Adjusting for confounders, BF was associated with a reduced risk of HF at age 6-10 (OR 0.71 (95% CI 0.57-0.87)) but not at age 13-18 (0.97 (0.79-1.18)). For RC and SRC, no significant associations were found, with ORs of 0.96 (0.77-1.11) and 0.86 (0.56-1.31) at age 6-10, and 1.04 (0.83-1.30) and 1.08 (0.70-1.67) at age 13-18, respectively   Conclusion   Our study does not provide clear evidence for a protective effect of breastfeeding against development of allergic RC. The disparity between results for HF and symptoms of RC might reflect different underlying conditions (allergic versus not allergic) and requires further examination.   Funding   SNF 32003B-144068; SNF PDFMP3-123162; Asthma UK 07/048.
Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment
Authors: Thomas A. Davis, Antonio J. Grillo-López, Christine A. White, Peter McLaughlin, Myron S. Czuczman, Brian K. Link, David G. Maloney, Robin L. Weaver, Jay Rosenberg, Ronald Levy
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This phase II trial investigated the safety and efficacy of re-treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low-grade or follicular non-Hodgkin’s lymphoma who relapsed after a response to rituximab therapy. PATIENTS AND METHODS: Fifty-eight patients were enrolled onto this study, and two were re-treated within the study. Patients received an intravenous infusion of 375 mg/m 2 of rituximab weekly for 4 weeks. All patients had at least two prior therapies and had received at least one prior course of rituximab, with a median interval of 14.5 months between rituximab courses. RESULTS: Most adverse experiences (AEs) were transient grade 1 or 2 events occurring during the treatment period. Clinically significant myelosuppression was not observed; hematologic toxicity was generally mild and reversible. No patient developed human antichimeric antibodies after treatment. The type, frequency, and severity of AEs in this study were not apparently different from those reported in the phase III trial of rituximab. The overall response rate in 57 assessable patients was 40% (11% complete response and 30% partial responses). Median time to progression (TTP) in responders and median duration of response (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months), respectively. These estimated medians are longer than the medians achieved in the patients’ prior course of rituximab (TTP and DR of 12.4 and 9.8 months, respectively, P &gt; .1) and in a previously reported phase III trial (TTP in responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing in seven of 23 responders. CONCLUSION: In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure.
Abstract 13760: Dipeptidyl-Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Prevented the Progression of Established Atheromatous Plaques in ApoE Deficient Mice - Possible Involvement of AMP-Activated Protein Kinase Pathway -
Authors: Hirofumi Kurokawa, Seigo Sugiyama, Koichi Sugamura, Junichi Matsubara, Koichiro Fujisue, Keisuke Ohba, Hirofumi Maeda, Eiichirou Yamamoto, Kenichi Tsujita, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2014)

Background: We demonstrated that dipeptidyl-peptidase-4 inhibitor (DPP4i) Des-Fluoro-Sitagliptin (DFS) exhibited anti-atherosclerotic effects on the newly development process of atherosclerosis, however it is unknown whether DPP4i also have anti-atherosclerotic effects on the established atheroma (preventing progression or regression). In the practical situation, it is clinically important to investigate whether DPP4i have beneficial effects on the established atherosclerosis. Methods and Results: 8 weeks old ApoE deficient mice were fed by high fat diet (HFD) for 12 weeks lead to development of the established atherosclerotic plaques, followed by randomized into 4 groups; continued HFD arm [HFD alone, HFD+DFS (200mg/kg/day)] and lipid-lowering arm [low fat diet (LFD) alone, LFD+DFS], for additional 8 weeks. DFS significantly reduced the progression of established plaque compared to HFD alone [plaque area per aorta; HFD (n=11): 53.3±4.9% vs. HFD+DFS (n=15): 43.8±9.0%, p&lt;0.05]. During the lipid-lowering therapy by diet, DFS supported the diet-induced regression of atherosclerosis [baseline 20 weeks old (n=10): 34.6±11.4%, LFD (n=17): 32.7±7.8% vs. LFD+DFS (n=18): 30.2±9.1%]. In vitro, DFS with glucagon-like peptide-1 (GLP-1) increased the phosphorylation of AMPK in human coronary artery endothelial cells (HCAEC) (2.71±0.31 fold, p&lt;0.01) and in THP-1-drived human macrophages (1.29±0.07 fold, p&lt;0.05). DFS with GLP-1 reduced the expression of adhesion molecules induced by tissue necrosis factor-α (intercellular adhesion molecule-1: -18.1±2.6%, p&lt;0.05, vascular cell adhesion molecule-1: -22.4±4.5%, p&lt;0.05), and these effects were abolished by AMPK inhibitor (Compound-C; CC) in HCAEC. In macrophages, DFS with GLP-1 reduced expression of the M1 pro-inflammatory factor (interleukin (IL)-1β; 0.74±0.04 fold, p&lt;0.05) but not the M2 anti-inflammatory factor (IL-10; 1.00±0.06 fold, p=0.99) and the effect on M1 was abolished by CC. Conclution: DFS exhibited beneficial effects on the established atherosclerosis with attenuating progression and supporting regression by the lipid-lowering therapy. AMPK activation by DFS might partly play a role in these processes. DFS could also be effective for the established atherosclerosis.
Original Article : Prevalence of IgG anti-HAV in patients with chronic hepatitis B and in the general healthy population in Korea
Authors: Sang Ho Lee, Hyoung Su Kim, Kwon Oh Park, Jong Won Park, Seung Yeon Chun, Seung Jin Lim, Hyun Jung Cho, Sung Jun Kim, Hye Won Park, Han Kook Moon, Woon Geon Shin, Kyung Ho Kim, Myoung Kuk Jang
Journal: Clinical and Molecular Hepatology (2010)

Background/Aims: Few studies have investigated hepatitis A virus (HAV) seroepidemiology in Koreans with chronic liver disease (CLD). This study compared the prevalence of IgG anti-HAV between the general healthy population and patients with hepatitis B virus-related CLD (HBV-CLD), with the aim of identifying predictors of HAV prior exposure. Methods: In total, 1,319 patients were recruited between June 2008 and April 2010. All patients were tested for IgG anti-HAV, hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus. The patients were divided into the general healthy population group and the HBV-CLD group based on the presence of HBsAg. The seroprevalence of IgG anti-HAV was compared between these two groups. Results: The age-standardized seroprevalence rates of IgG anti-HAV in the general healthy population and patients with HBV-CLD were 52.5% and 49.1%, respectively. The age-stratified IgG anti-HAV seroprevalence rates for ages ≤19, 20-29, 30-39, 40-49, 50-59, and ≥60 years were 14.3%, 11.2%, 45.5%, 90.5%, 97.6% and 98.3%, respectively, in the general healthy population, and 0%, 9.8%, 46.3%, 91.1%, 97.7%, and 100% in the HBV-CLD group. In multivariate analysis, age (<30 vs. 30-59 years: OR=19.339, 95% CI=12.504-29.911, P<0.001; <30 vs. ≥60 years: OR=1060.5, 95% CI=142.233-7907.964, P<0.001) and advanced status of HBV-CLD (OR=19.180, 95% CI=4.550-80.856, P<0.001) were independent predictors of HAV prior exposure. Conclusions: The seroprevalence of IgG anti-HAV did not differ significantly between the general-healthy-population and HBV-CLD groups. An HAV vaccination strategy might be warranted in people younger than 35 years, especially in patients with HBV-CLD. (Korean J Hepatol 2010;16:362-368)
Abstract 091: Mitochondrial Calcium Currents Are Conducted By A Pore Encoded By The MCU Gene.
Authors: Dipayan Chaudhuri, Yasemin Sancak, Vamsi K Mootha, David E Clapham
Journal: Circulation Research (2013)

Mitochondrial uptake of calcium (Ca 2+ ) in cardiomyocytes is thought to regulate cell survival and match ATP production to energetic demands. Of multiple pathways allowing such entry, the mitochondrial Ca 2+ uniporter is a highly Ca 2+ -selective channel encoded by several recently-discovered genes. However, which of these several genes encodes the pore-forming subunit of the channel remains an open question. Using whole-mitoplast voltage-clamping, we show that RNAi-mediated knockdown of the mitochondrial calcium uniporter ( MCU ) gene reduces the uniporter current ( I MiCa ), whereas overexpression increases it. Mutations in the putative pore domain alter key features of I MiCa , such as its strong affinity for ruthenium red, a classic uniporter blocker. These analyses demonstrate that MCU encodes the pore-forming subunit of the uniporter channel.
Disseminated tumor cells (DTC) in bone marrow (BM) and clinical outcome: Final results of pooled analysis on 10-year survival of 4,703 breast cancer patients
Authors: S. Braun, F. D. Vogl, K. Pantel
Journal: Journal of Clinical Oncology (2005)

502 Background: Statistically powerful prognostic data on long-term outcome of DTC +ve breast cancer patients is needed to enable evidence-based therapeutic strategies designed to improve patient outcome. Methods: Individual patient data of 9 studies, involving 4,703 patients with stage I-III breast cancer, were combined to analyze long-term clinical outcome. A time-stratified Cox multivariable regression model was required because hazard ratios were not constant over the full length of the 10-year period. Results: The prevalence of DTC was 30.6%, and was significantly associated with larger tumor size, high grade, lymph-node metastasis (each P<0.001) and endocrine non-responsiveness (P=0.003). In the final multivariable model, DTC was an independent prognostic variable for early relapse and death. During the first 5 years of follow-up and thereafter, hazard ratios (HR) for OS were 1.81 (95%CI 1.51–2.16; P<0.001) and 1.58 (95% CI 1.12–2.22; P=0.009), respectively. Early relapse occurred significantly more often among DTC +ve patients (log rank, each P<0.001), with a multivariable HR of 1.85 (95%CI 1.58–2.14) for DFS and 2.03 (95%CI 1.72–2.39) for DDFS during the initial 5 years of follow-up. DTC was not an independent predictor for DFS and DDFS after 5 years. On univariate analysis, OS was significantly reduced for DTC +ve patients among subgroups on either endocrine therapy (n=1,499; incidence rate ratio [IRR] 2.49, 1.83–3.37; P<0.001) or chemotherapy alone (n=1,596; IRR 2.26, 1.80–2.85; P<0.001). Moreover, among 1,036 patients with pT1N0 disease, who received no systemic adjuvant treatment, those 229 DTC +ve patients had significantly worse OS (P=0.001), DFS (P=0.014) and DDFS (P=0.007), as compared to 807 DTC -ve patients. Conclusions: Presence of DTC is a strong prognostic factor of level I evidence for poor clinical outcome. Since for patients with DTC in BM it is reasonable to assume a differential susceptibility to current adjuvant therapy, as shown overall and in subgroups, consideration of DTC for clinical decision making might enable improved risk stratification in future clinical trials. No significant financial relationships to disclose.
Coordinate older age care around people, not services, says report
Authors: Gareth Iacobucci
Journal: BMJ (2016)

An independent commission has called for radical transformation in the way that urgent care is delivered to older people in England to ensure that it is tailored more sensitively to patients’ individual needs.

In a new report published on 28 January,1 the Commission on Improving Urgent Care for Older People set out eight key principles that it thinks the NHS and social care services should adopt to improve urgent care for older people and relieve the growing pressure …
Relationship between sympathetic activity and blood pressure in OSA patients
Authors: Renaud Tamisier, Donato Lacedonia, Jean-Philippe Baguet, Jean-Louis Pepin, Patrick Levy
Journal: European Respiratory Journal (2013)

Obstructive sleep apnea syndrome (OSAS) is associated with high Sympathetic Activity (SA) and a subsequent risk of hypertension and atherosclerosis. Objectives of this study were to assess the relationship between SA, Blood Pressure (BP) and early cardiovascular disease markers in OSA

We studied 38 OSA patients and 17 aged-matched controls. OSA patients were otherwise healthy, without evidence of clinic hypertension. SA was measured by direct peroneal microneurography: Muscle Sympathetic Nerve Activity (MSNA) and all subjects underwent a full polysomnography, 24h Ambulatory Blood Pressure Monitoring (ABPM), arterial stiffness by Pulse Wave Velocity (PWV), vascular reactivity by Peripheral Arterial Tone (PAT) and arterial carotid Intima Media Thickness (IMT).

Groups were comparable for all but not for BMI (25.92 ± 2.71 vs 24.20 ± 2.39 kg/m², p= 0.02). Office Systolic and diastolic BP were the same in patients and controls, while on ABPM 24h-diastolic BP was higher in OSAS group (79.92 ± 8.73 vs 74.59 ± 8.83, p=0.046). There was a strong correlation between SA and all BP parameters: systolic and diastolic office BP (R=0.39 and 0.42,p<0.01) and systolic and diastolic 24-ABPM (R=0.38 and 0.46, p<0.001). Burst/min were correlated with PWV and IMT (R=0.52; p=0.036). Preliminary data on 15 OSA and 9 controls were obtained after 6 month and show that CPAP treatment reduced: SA (Bursts/min 40.49 ± 10.63 vs 35.47 ± 10.06, p<0.05), Diurnal DBP (86.86±11.97 vs 82.07±11.12, P=0.03) and nocturnal dipping (-17.14±5.33 vs -11.07±3.54, P=0.002)

In “Healthy” OSAS SA is likely to play a role in the pathogenesis of hypertension and atherosclerosis. SA reduction induced by CPAP, may reduce the risk of cardiovascular diseases.
Digital versus screen film mammography: Impact on positive predictive values following transition.
Authors: Elizabeth Roy, David Motiuk, Paul Burrowes, Bobbie Docktor
Journal: Journal of Clinical Oncology (2012)

12 Background: The Calgary Health Region changed from screen film mammography (SFM) to digital mammography (DM) in 2005. This retrospective study was designed to determine the effect of this conversion on positive predictive values (PPV) for cancerous and precancerous breast lesions. Methods: In the Calgary region, biopsies for mammographic calcifications are only done at Foothills Medical Centre (FMC) by a small group of mammographers employing homogeneous techniques. From FMC’s database, we reviewed core biopsy data for mammographic calcifications in the years 2002-2004 (SFM years) and 2008-2010 (DM years). Mammographic masses were excluded. We determined PPVs for each set of years for detection of cancerous lesions (PPV 3 for calcifications). We further calculated the PPVs of SFM and DM for detection of high-risk lesions, including ADH, ALH, LCIS, and papilloma collectively (precancerous lesions). The detection rates of benign lesions (excluding precancerous lesions) after biopsy were also determined. Statistical analysis was performed using two-tail z-tests. Results: 3,778 biopsies in 3,544 patients were reviewed. The difference in overall detection rate of cancer after biopsy for mammographic calcification between SFM (PPV 3 = 24.7%) and DM (PPV 3 = 23.8%) was not statistically significant (p = .53). On further analysis, the PPV for precancerous lesions increased (p &lt; .0001) in DM (11.6%) versus SFM (7.8%). No significant difference (p = .065) was found in detection of benign lesions. Conclusions: In comparing DM to SFM, we found no significant change in PPV 3 with respect to calcifications. However, with DM, there was a statistically significant increase in detection of lesions considered at risk for future malignancy. Given that the natural history of these premalignant lesions is incompletely understood, the significance of this finding is in question. This potential trend could be further strengthened by determining PPV 1 for cancerous and precancerous lesions with respect to calcifications. [Table: see text]
Whole Transcriptome Sequencing In Refractory T-Cell Acute Lymphoblastic Leukemia
Authors: Valentina Gianfelici, Sabina Chiaretti, Zeynep Kalender Atak, Fulvia Brugnoletti, Messina Monica, Gert Hulselmans, Kim de Keersmaecker, Ellen Geerdens, Marco Mancini, Antonella Vitale, Loredana Elia, Mabel Matarazzo, Davide Rossi, Gianluca Gaidano, Anna Guarini, Stein Aerts, Jan Cools, Robin Foà
Journal: Blood (2013)
Systemic administration of mutant vesicular stomatitis virus (VSV) completely eradicates nasopharyngeal carcinoma (NPC) models
Authors: Nehad M. Alajez, Joseph D. Mocanu, Shane Knowles, John C. Bell, Fei-Fei Liu
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2177 

Introduction: Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck region with unique clinical and demographic features. Standard therapy for NPC achieves only modest survival rates, underscoring a need to develop novel therapies. Our group has previously investigated multiple novel molecular therapeutics including adenoviral vectors, and antisense oligonucleotide approaches. None has succeeded in complete eradication of established xenograft tumours. Hence, we were interested in examining the therapeutic potential of vesicular stomatitis viruses (VSV), which preferentially replicate in malignant cells, presumably due to defects in their interferon (IFN) signaling. Materials and Methods: Two EBV-positive human NPC models were utilized: the C666-1, and the C17 tumours. The MTS assay was utilized to assess viability in vitro ; apoptosis was measured using flow-based techniques including fraction of cells in the sub-G0/G1 phase, and caspase-3 activation. In vivo experiments were conducted using nu/nu mice, which are permissive to VSV infection. The VSV-delta51-GFP is a mutant VSV carrying the GFP reporter gene; control VSV was inactivated by UV radiation (30 min in laminar flow hood). Results: Our data demonstrated that VSV-delta51-GFP (MOI = 0.00001 to 10.0) was cytotoxic to C666-1 cells in a time and dose-dependent manner (75.4 to 87.2 killing at 72 hrs, respectively). Control VSV demonstrated no cytotoxicity. VSVdelta51 infection of C666-1 cells at MOI=1.0 induced apoptosis in > 6.2% of infected cells at 24 hrs and reached >10.8 % at 72 hrs. C666-1 cells (5x10^6) infected ex vivo with VSVdelta51-GFP (MOI=5.0) and then implanted into nu/nu mice demonstrated no tumour formation when injected subcutaneously, followed for 58 days, while C666-1 cells infected with UV-irradiated control virus formed tumors as early as day 27 post injection. Therapeutic efficacy of VSVdelta51-GFP was evaluated in both the C666-1 and C17 models. Four intravenous injections of VSVdelta51-GFP (5x1^8 pfu x 4) were able to completely eradicate established tumours followed for 31 days. No adverse effects were observed in mice treated with VSV; control VSV demonstrated no in vivo effect. Conclusion: These data demonstrate that VSV is a potentially promising novel oncolytic viral therapeutic modality for NPC. We are currently investigating the therapeutic benefit of combining VSV with RT and chemotherapy, and anticipate application to human patients in the near future if the combinatorial strategy demonstrates such impressive efficacy. Our finding may also be applicable to other human cancers.
P0219 : Prophylactic administration of blood products does not prevent bleeding after endoscopic band ligation of varices
Authors: A. Blasi, R. Risco, A. Fernandez Simon, C. Rodriguez de Miguel, A. Diaz-Gonzalez, A. Mendez-Bocanegra, J. Llach, A. Cardenas, G. Martinez
Journal: Journal of Hepatology (2015)