tbuckley/cabot-search huggingface dataset:
Epidermal growth factor receptor (EGFR) mRNA expression levels are strongly correlated between primary colorectal cancer and corresponding liver metastases
Authors: H. Kuramochi, K. Hayashi, K. Uchida, M. Yamamoto, K. D. Danenberg, P. V. Danenberg
Journal: Journal of Clinical Oncology (2007)

4106 Background: As it has been well known that epidermal growth factor receptor (EGFR) is strongly related to a tumor proliferation and a metastasis, new EGFR-inhibitory small molecules, such as gefitinib and erlotinib, and EGFR antibodies have been developed recently. It is reported that the high expression levels of EGFR mRNA are associated with high response probability and longer progression-free survival in gefitinib-treated lung cancer patients. Thus, since liver metastases are the main cause of death for most of colorectal cancer (CRC) patients, it is reasonable to expect that measurement of EGFR gene expression levels in liver metastases would provide the best prediction of therapy benefit, but in most cases, only biopsies of the patient’s primary tumor are readily available for analysis. Our aim was to determine how EGFR gene expression levels in primary CRC were related to those in liver metastases. Methods: Thirty-one pairs of primary CRC and corresponding liver metastases were analyzed. (18 males and 13 females: Median age 66 (range 45–85)). Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR (Taqman PCR). Results: No significant difference was seen between median mRNA expression levels of EGFR in primary cancer and those in corresponding liver metastases (Median value: 1.35 vs 1.24, p=0.99 , Wilcoxon signed rank test), although the median value of EGFR mRNA from normal liver tissue is significantly higher than those from normal colon mucosa (Median value: 5.06 vs 1.39, p&lt;0.0001). When matched tissue sets were compared on an individual basis, there was a significant correlation for EGFR mRNA expression between primary cancer and corresponding liver metastases (rs=0.78, p&lt;0.0001, Spearman rank correlation coefficient). Conclusions: A good prediction of EGFR mRNA levels in liver metastases can be obtained by measuring those of primary CRC. No significant financial relationships to disclose.
A Decade of Changes in Preferences for Life-Sustaining Treatments Among Terminally Ill Patients With Cancer
Authors: Siew Tzuh Tang, Tsang-Wu Liu, Fur-Hsing Wen, Chiun Hsu, Yi-Heng Chang, Cheng-Shyong Chang, Yung-Chuan Sung, Cheng-I Hsieh, Shou-Yi Chang, Li Ni Liu, Ming-Chu Chiang
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Changes over time in preferences for life-sustaining treatments (LSTs) at end of life (EOL) in different patient cohorts are not well established, nor is the concept that LST preferences represent more than 2 groups (uniformly prefer/not prefer). Purpose: The purpose of this study was to explore heterogeneity and changes in patterns of LST preferences among 2 independent cohorts of terminally ill patients with cancer recruited a decade apart. Methods: Preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, nasogastric tube feeding, and dialysis were surveyed among 2,187 and 2,166 patients in 2003–2004 and 2011–2012, respectively. Patterns and changes in LST preferences were examined by multigroup latent class analysis. Results: We identified 7 preference classes: uniformly preferring, uniformly rejecting, uniformly uncertain, favoring nutritional support but rejecting other treatments, favoring nutritional support but uncertain about other treatments, favoring intravenous nutritional support with mixed rejection of or uncertainty about other treatments, and preferring LSTs except intubation with mechanical ventilation. Probability of class membership decreased significantly over time for the uniformly preferring class (15.26%–8.71%); remained largely unchanged for the classes of uniformly rejecting (41.71%–40.54%) and uniformly uncertain (9.10%–10.47%), and favoring nutritional support but rejecting (20.68%–21.91%) or uncertain about (7.02%–5.47%) other treatments, and increased significantly for the other 2 classes. The LST preferences of Taiwanese terminally ill patients with cancer are not a homogeneous construct and shifted toward less-aggressive treatments over the past decade. Conclusions: Identifying LST preference patterns and tailoring interventions to the unique needs of patients in each LST preference class may lead to the provision of less-aggressive EOL care.
Oxaliplatin (with 5FU and leucovorin ) in patients above age 70 ( «elderly» ) suffering from metastatic colorectal cancer: An observational study
Authors: B. Exquis, M. Aapro, S. Kohler
Journal: Journal of Clinical Oncology (2004)

8042 Background: Data on standard chemotherapy in the real elderly are rare. Patients and Methods: We conducted, during 18 months, an observational study of Oxaliplatin in combination with 5-FU and leucovorin (FUFOL) for treatment of metastatic colorectal cancer, in order to assess safety, response rate and exact regimens used in patients below and above 70 years. Twenty-five centres documented 137 patients (57% male, median age 62 years, colon/rectum/other: 64%/30%/6%, ECOG PS 0/1/2/3: 34%/55%/10%/1%, previous chemotherapy: 69%). Total number of administered cycles was 816 (median 6, range 1–23). Results: \(\underline{\mathrm{Regimen\ used}}\): 71% received Eloxatin at 85mg/m2 every 2 weeks, 18% at 130mg/m2 every 3 weeks, and 11% received other regimens. FUFOL regimens were 37% FOLFOX4, 27% simplified 46h infusion, 21% weekly bolus (Roswell Park), 8% daily bolus (Mayo), 7% others. \(\underline{\mathrm{Response\ rates}}\): CR 4%, PR 21%, SD 37, PD 27%, unknown 11%. ECOG PS before vs. after therapy: 20% of patients improved, 62% stable, 18% deteriorated. \(\underline{\mathrm{Safety}}\): Grade 3/4 toxicities (per cycle) were nausea (0.1%), vomiting (0.5%), diarrhea (2%), stomatitis (0.2%), thrombocytopenia (1%), leucocytopenia (1%), granulocytopenia (0.6%), lymphocytopenia (7.2%). 75% no hair loss, 18% had mild and 7% had grade 2 hair loss. Grade 3 neuropathy (Levy scale) was reported by 3%. These 4 patients had at least tumor stabilisation or partial response. \(\underline{\mathrm{Influence\ of\ age}}\): 33 patients were older than 70. Overall response rate was 24% for patients up to 70 years and 27% for older patients. Grade 3/4 toxicities (per cycle) were (≤70/>70 years): nausea 0.3%/0.0%, vomiting 0.7%/0.0%, diarrhea 1.8%/2.8%, stomatitis 0.4%/0.0%, neuropathy 0.7%/0.0%. Conclusion: Combination therapy with Eloxatin as used here is safe and efficacious in daily practice. Elderly patients benefit equally from therapy without increased toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo
Reduction in climate pollutants could save five million lives a year, WHO report says
Authors: Anne Gulland
Journal: BMJ (2015)

Reducing emissions of black carbon, ozone, and methane could save millions of lives a year, a new report by the World Health Organization has found.1

The report said that exposure to outdoor air pollution is estimated to cause around 3.7 million premature deaths a year, and 4.3 million deaths a year are attributed to household air pollution from burning solid fuel. Diseases caused by exposure to these pollutants include: ischaemic heart disease, which is responsible for more than 2.6 million deaths a year; stroke (2.97 million deaths); chronic obstructive pulmonary disease (966 900); and lung …
Coordinate Morphological and Biochemical Interconversion of Human Neuroblastoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R A Ross, B A Spengler, J L Biedler
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article Coordinate Morphological and Biochemical Interconversion of Human Neuroblastoma Cells Get access Robert A. Ross, Robert A. Ross Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara A. Spengler, Barbara A. Spengler Search for other works by this author on: Oxford Academic PubMed Google Scholar June L. Biedler June L. Biedler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 71, Issue 4, October 1983, Pages 741–747, https://doi.org/10.1093/jnci/71.4.741 Published: 01 October 1983 Article history Received: 14 March 1983 Accepted: 31 May 1983 Published: 01 October 1983
A survey of best practices for RNA-seq data analysis
Authors: Ana Conesa, Pedro Madrigal, Sonia Tarazona, David Gomez-Cabrero, Alejandra Cervera, Andrew McPherson, Michał Wojciech Szcześniak, Daniel J. Gaffney, Laura L. Elo, Xuegong Zhang, Ali Mortazavi
Journal: Genome biology (2016)

RNA-sequencing (RNA-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping. We highlight the challenges associated with each step. We discuss the analysis of small RNAs and the integration of RNA-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics.
Abstract 9951: Cardiac GRK2 Inhibition via ARKct Augments 2-adrenergic Receptor-dependent Contractility and Survival Post-Myocardial Infarction
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Ashley Bathgate, Walter J Koch
Journal: Circulation (2012)

Rationale: β 1 and β 2 -adrenergic receptors (βARs) play distinct roles in the heart, e.g. β 1 AR is pro-contractile and pro-apoptotic but β 2 AR anti-apoptotic and only weakly pro-contractile. G protein coupled receptor kinase (GRK)-2 desensitizes and opposes βAR pro-contractile signaling by phosphorylating the receptor and inducing beta-arrestin (βarr) binding. We posited herein that GRK2 blockade in vivo might enhance the pro-contractile and anti-apoptotic signaling of the cardiac β 2 AR. Objective: We tested the effects of cardiac-targeted GRK2 inhibition in vivo exclusively on β 2 AR signaling post-myocardial infarction (MI). Methods and Results: We crossed β 1 AR knockout (B1KO) mice with cardiac-specific transgenic mice expressing the βARKct, a peptide inhibitor of GRK2, and studied the offspring under normal conditions and post-MI. βARKct expression in vivo leads to significantly enhanced β 2 AR-dependent cardiac function, in part via reduction of phosphodiesterase (PDE)4D recruitment to the receptor (ejection fraction in sham-operated, healthy mice: 70+1.1% in βARKct/B1KO`s vs. 59+1.77% in B1KO`s, p&lt;0.05, n=7, and in 4-week post-MI mice: 41.3+3% in βARKct/B1KO`s vs. 25+1.2% in B1KO`s, p&lt;0.05, n=7). In addition, βARKct/B1KO`s have decreased heart dilatation and infarct size, and increased survival at 4 weeks post-MI compared to control B1KO mice. These phenotypic effects are secondary to decreased apoptosis (mediated by Bcl-2 elevation) and increased wound healing-associated inflammation (mediated by NF-κB activation) in βARKct/B1KO hearts very early (at 24 hrs) post-MI vs. B1KO controls. Conclusions: GRK2 inhibition via βARKct markedly augments cardiac β 2 AR beneficial (pro-contractile and anti-apoptotic) signaling post-MI, and thus might be useful for β 2 AR agonist drug therapy in heart failure, e.g. in post-MI patients awaiting cardiac transplantation.
Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group.
Authors: M Schumacher, G Bastert, H Bojar, K Hübner, M Olschewski, W Sauerbrei, C Schmoor, C Beyerle, R L Neumann, H F Rauschecker
Journal: Journal of Clinical Oncology (1994)

PURPOSE In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities. PATIENTS AND METHODS During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91). Until March 31, 1992, median follow-up time was 56 months with 197 events for disease-free survival and 116 deaths observed. This provides a power of approximately 80% to detect a potential treatment difference corresponding to a relative risk (RR) of 0.67 for recurrence-free survival. Treatment modalities and various patient characteristics were evaluated by means of a multivariate Cox regression analysis. RESULTS No significant difference in recurrence-free survival was observed with respect to hormonal therapy (RR = 0.75 TAM v no TAM; 95% confidence interval [CI], 0.54 to 1.04; P = .08) as well as duration of chemotherapy (RR = 0.90 of 6 x CMF v 3 x CMF; 95% CI, 0.67 to 1.19; P = .45). Similar results were obtained for overall survival. The multivariate analysis revealed a significant prognostic impact of the number of positive lymph nodes and the progesterone receptor level on recurrence-free survival. Compliance with chemotherapy within the range of 85% to 115% of the target dose was achieved in 94% and 78% of the patients randomized to 3 x CMF and 6 x CMF, respectively. Sufficient compliance with TAM was reported for 141 patients (93%). CONCLUSION At this stage of follow-up, six courses of CMF are not superior to three courses with respect to recurrence-free survival.
525 TENOFOVIR MONOTHERAPY FOR NAÏVE PATIENTS WITH CHRONIC HEPATITIS B: A MULTICENTER EUROPEAN STUDY IN CLINICAL PRACTICE IN 302 PATIENTS FOLLOWED FOR 30 MONTHS
Authors: P. Lampertico, R. Soffredini, M. Viganò, C. Yurdaydin, R. Idilman, G. Papatheodoridis, M. Ekaterini, M. Buti, R. Esteban, S. Zaltron, A. Vavassori, G. Carosi, E. Minola, M. Vinci, G. Pinzello, A. Giorgini, M. Zuin, A. Salmi, P. Del Poggio, F. De Filippi, S. Bruno, L. Pasulo, S. Fagiuoli, M. Andreoletti, A. Colli, F. Fumagalli Maldini, M. Milanese, A.E. Colombo, G. Bellati, E. Angeli, C. Magni, G. Gubertini, G. Rizzardini, M. Fasano, T. Santantonio, N. Terreni, G. Spinzi, F. Facchetti, F. Invernizzi, M. Colombo
Journal: Journal of Hepatology (2012)
Assessment of frozen glove use in the prevention of docetaxel induced onycholysis and cutaneous reaction. Results of a multicenter case-control study
Authors: F. Scotte, J. M. Tourani, E. Banu, M. Peyromaure, A. Jenabian, E. Levy, K. Coquelin, E. Magherini, S. Marsan, S. Oudard
Journal: Journal of Clinical Oncology (2004)

8003 Background: Onycholysis and skin toxicity occur in about 15% of patients (pts) treated with docetaxel (D). We investigated the efficacy and safety of an Elasto-Gel (Akromed, France) flexible frozen glove (FG) for the prevention of D-induced onycholysis and skin toxicity. Methods: Cancer pts receiving D at 75 mg/m2 (1 hour infusion q3w) alone or in combination chemotherapy were eligible for this matched case-control study. Each patient wore a FG for a total of 90 minutes (min) on the right hand (15 min before, during D administration, and 15 min after). The left hand was not protected by FG and acted the control. Onycholysis and skin toxicity were assessed at each cycle by NCI-CTC v.2 criteria and documented by photography. Wilcoxon matched-pairs ranks test was used to determine the magnitude of difference between two matched groups. Results: Between Aug 2002 and Sept 2003, 45 pts were evaluated: median age 65 years, M/F: 35/10, performance status 0/1/2 (%) = 52/41/7, cancer type (prostate: 58%, lung: 24%, breast: 11%, others: 7%), D monotherapy 72%. Onycholysis and skin toxicity (main criteria) was significantly lower in the FG protected hand compared with the control hand (p=0.0001, Wilcoxon test). Onycholysis was grade (G)0: 89% vs 49% and G1–2: 11% vs 51% in the FG-protected hand and the control hand, respectively. Skin toxicity was G0: 73% vs. 41% and G1–2: 27% vs. 59% in the FG-protected hand and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between FG-protected and the control hand, respectively [106 days (5 cycles) vs. 58 days (2.7 cycles) for nail toxicity; 57 days vs. 58 days for skin toxicity]. Five pts (11%) experienced discomfort due to cold intolerance of the FG protected hand. Conclusions: Frozen glove significant reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management for a better patient's quality of life. No significant financial relationships to disclose.
Providing accessible healthcare to migrants is morally right and cost effective
Authors: Jessica L Potter
Journal: BMJ (2015)

Keith and Van Ginneken highlight an important matter.1 Research agrees that the introduction of fees for migrants probably impedes access to healthcare, infringes on the international human rights agreement, and delays care, thereby increasing costs and threatening public health. Interviewed experts suggest the Immigration Act is a way for the government to show it is tough on immigration and is based …
Bevacizumab (Bev) combined with either capecitabine (X) or weekly paclitaxel (Pac) as first-line chemotherapy (CT) for HER2-negative, locally recurrent or metastatic breast cancer (LR/MBC): Preliminary safety data from the CECOG phase III TURANDOT trial.
Authors: I. Lang, M. J. Inbar, R. Greil, G. G. Steger, S. Beslija, Z. Kahan, A. E. Eniu, Z. Zvirbule, D. E. Sirbu, C. Zielinski
Journal: Journal of Clinical Oncology (2010)

1126 Background: The combination of Bev with first-line X or taxane-based therapy significantly improves progression-free survival (PFS) in LR/MBC. This phase III, randomized study is to determine the efficacy of Bev+Pac vs Bev+X in this setting. Methods: Patients with HER2-negative, chemonaïve LR/MBC and ECOG PS 0–2 are eligible. Prior (neo)adjuvant CT is permitted if completed ≥6 months before randomization (≥12 months for taxane-containing therapy). Pts are randomized to Bev+X (X 1,000mg/m2 bid d1–14 + Bev 15mg/kg d1, q21d) or Bev+Pac (Pac 90mg/m2 d1, 8, 15 + Bev 10mg/kg d1,15, q28d), with treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Primary endpoint is non-inferiority in overall survival with Bev+X vs Bev+Pac and recruitment target is 560 pts. This planned interim safety analysis includes pts randomized by July 31, 2009 who are eligible for the safety analysis (ie. post-baseline safety data available). Results: 174 pts have been randomized, 167 are eligible for analysis (median age 58 years [range: 31–77]): Bev+Pac n=87, Bev+X n=80. Most pts were postmenopausal (83%), with estrogen receptor-positive (77%) and progesterone receptor-positive (64%) disease, and ECOG PS 0 (71%); 50% had received prior adjuvant CT. 155 pts received ≥2 cycles of Bev therapy, as required per protocol. Median (range) number of 4-week Bev+Pac cycles administered was 4 (1–11) of Pac and 4 (1–12) of Bev. Median (range) number of 3-week Bev+X cycles administered was 6 (1–14) of X and 6.5 (1–14) of Bev. Adverse events (AEs) were observed in 82% and 80% of pts in the Bev+Pac and Bev+X groups, including grade ≥3 AEs in 32% and 31%, and serious AEs in 13% and 10%, respectively. The most frequent grade 3/4 AEs were neutropenia (13.8%) with Bev+Pac and diarrhea (8.8%) with Bev+X. Conclusions: With neutropenia and gastrointestinal disturbance representing the most frequent grade 3/4 AEs with Bev+Pac and Bev+X, respectively, preliminary safety data are in accordance with previously published safety data for these combinations and no safety concerns have been raised. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Roche Bristol-Myers Squibb, Roche Bristol-Myers Squibb, Roche
A nationwide survey of hepatitis E viral infection in French blood donors
Authors: Jean Michel Mansuy, Pierre Gallian, Chloé Dimeglio, Karine Saune, Catherine Arnaud, Bertrand Pelletier, Pascal Morel, Dominique Legrand, Pierre Tiberghien, Jacques Izopet
Journal: Hepatology (2016)

Most cases of hepatitis E viral (HEV) infection in developed countries are autochthonous. Nevertheless, the reported seroprevalence of HEV varies greatly depending on the geographical area and the performance of the immunoassay used. We used validated assays to determine the prevalence of anti‐HEV immunoglobulin G (IgG) and IgM among 10,569 French blood donors living in mainland France and three overseas areas. Epidemiological information was collected using a specific questionnaire. We found an overall IgG seroprevalence of 22.4% (8%‐86.4%) depending on the geographical area ( P &lt; 0.001). The presence of anti‐HEV IgG was associated with increasing age ( P &lt; 0.001) and eating pork meat ( P = 0.03), pork liver sausages ( P &lt; 0.001), game meat ( P &lt; 0.01), offal ( P &lt; 0.001), and oysters ( P = 0.02). Conversely, drinking bottled water was associated with a lower rate of anti‐HEV IgG ( P = 0.02). Overall IgM seroprevalence was 1% (0%‐4.6%). The frequency of anti‐HEV IgM was higher in donors living in a high anti‐HEV IgG seroprevalence area (1.9% versus 0.7%, P &lt; 0.001) and in those eating pork liver sausage (1.4% versus 0.7%, P &lt; 0.01), pâté (1% versus 0.4, P = 0.04), and wild boar (1.3% versus 0.7%, P &lt; 0.01). Conclusion: HEV is endemic in France and hyperendemic in some areas; eating habits alone cannot totally explain the exposure to HEV, and contaminated water could contribute to the epidemiology of HEV infection in France. (H epatology 2016;63:1145–1154)