tbuckley/cabot-search huggingface dataset:
Antiangiogenic VEGF-Ax: A New Participant in Tumor Angiogenesis
Authors: Sandeepa M. Eswarappa, Paul L. Fox
Journal: Cancer Research (2015)

The transcript of the angiogenic factor vascular endothelial growth factor A (VEGF-A) is subject to a multitude of stimulus-dependent, posttranscriptional regulatory events, consistent with its unusually long 3' untranslated region. We have recently reported translational readthrough of VEGFA mRNA whereby translating ribosomes traverse the canonical stop codon to a conserved, downstream stop codon, generating VEGF-Ax ("x" for extended), a novel, extended isoform with an additional 22 amino acids appended at the C-terminus. This event is the first vertebrate example of protein-regulated, programmed translational readthrough that generates a protein with a known function. Remarkably, VEGF-Ax exhibits potent antiangiogenic activity, both in vitro and in vivo, thus raising profound clinical implications, particularly with respect to cancer treatment. In this review, we discuss the potential of VEGF-Ax as a therapeutic agent and drug target, as well as its possible role in the failure of, or resistance to, conventional anti-VEGF therapies in many types of cancers.
Downregulated BMPR2 signalling pathway in nitrofen-induced pulmonary hypoplasia
Authors: Martine Makanga, Céline Dewachter, Benoît Rondelet, Robert Naeije, Laurence Dewachter
Journal: European Respiratory Journal (2011)

Background:  Despite remarkable progress in resuscitation and intensive care, morbidity and mortality in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. However, pathogenesis associated with CDH is still not clearly understood. The bone morphogenetic protein receptor (BMPR) type 2 signaling pathway plays a crucial role in fetal lung development.   Hypothesis:  We sought to determine whether BMPR2 signaling pathway is altered in the nitrofen-induced pulmonary hypoplasia associated to CDH.   Methods:  Pregnant rats were exposed to either 100 mg nitrofen or olive oil on day 9 (D9) of gestation. At D17 and D19, embryos were delivered by cesarean and sacrificed to check if diaphragmatic hernia existed. Fetal lung, heart and liver tissue weights and body weight of each fetus were recorded. Lung tissue was harvested for pathobiological evaluation (by immunohistochemistry and RTQPCR).   Results:  Lung, heart and liver weight-to-body weight ratios decreased by 20, 30 and 25% (p   Conclusions:  In nitrofen-induced CDH, BMPR2 signaling pathway is downregulated in hypoplastic lungs at both early and late stages of lung development.
Population studied was peculiarly healthy and preoccupied with health
Authors: J Munby, D F Weetman
Journal: BMJ (1996)

Dietary fat and risk of coronary heart disease in menStudies quoted showed opposite of what is claimed EDITOR,-Alberto Ascherio and colleagues were unable to show a significant association between intake of saturated fatty acids (as percentage of energy) or of cholesterol and total myocardial infarction and coronary heart disease after
Abstract 1515: Simultaneous detection of KRAS and TP53 mutations in human cancer cell lines using multiplex qPCR
Authors: Sunali Patel, Cora Woo, Joyce Wilde, Sundiep Phanse
Journal: Cancer Research (2014)

Abstract Genetic alterations in KRAS and TP53 genes are common in many cancers and the understanding of their role in progression of cancer is vital for the design of successful treatment approaches. Studies suggest that mutations in KRAS and TP53 genes independently hindered the use of EGFR inhibiting drugs like Cetuximab (Erbitux) for the treatment of colorectal cancer (1). The genetic alterations in these genes are now routinely checked before starting any expensive treatments. Here, we successfully demonstrated use of duplex mutli-color SNP genotyping assays to detect KRAS and TP53 mutation in human colon cancer cell lines. This method can be potentially used to analyze samples with limited quantity and get as much information as possible from a single sample. To study the impact of these mutations, we generated gene expression profiles of 672 genes related to signaling pathways by using the Human signal transduction medium-throughput OpenArray® Panel. Selected cancer genes like BRAC1, BAX, CFLAR, MYC and others were evaluated using multiplexed single-tube PCR simultaneously detecting four different targets in the same sample. These results demonstrate that duplex SNP genotyping and multiplexed gene expression profiling from a single sample increases research capacity in situations when sample is limited. Reference: 1. A Oden-Gangloff, F Di Fiore, F Bibeau, A Lamy, G Bougeard, F Charbonnier, F Blanchard, D Tougeron, M Ychou, F Boissière, F Le Pessot, J-C Sabourin, J-J Tuech, P Michel and T Frebourg.TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy. British Journal of Cancer (2009) 100, 1330-1335 Citation Format: Sunali Patel, Cora Woo, Joyce Wilde, Sundiep Phanse. Simultaneous detection of KRAS and TP53 mutations in human cancer cell lines using multiplex qPCR. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1515. doi:10.1158/1538-7445.AM2014-1515
Impact of Neoadjuvant Chemotherapy on Postoperative Morbidity in Soft Tissue Sarcomas
Authors: Funda Meric, Mira Milas, Kelly K. Hunt, Kenneth R. Hess, Peter W. T. Pisters, Gerhard Hildebrandt, Shreyaskumar R. Patel, Robert S. Benjamin, Carl Plager, Nicholas E. J. Papadopolous, Michael A. Burgess, Raphael E. Pollock, Barry W. Feig
Journal: Journal of Clinical Oncology (2000)

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.
Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma.
Authors: S I Bearman, F R Appelbaum, A Back, F B Petersen, C D Buckner, K M Sullivan, H G Schoch, L D Fisher, E D Thomas
Journal: Journal of Clinical Oncology (1989)

Ninety-five patients transplanted for malignant lymphoma were retrospectively evaluated for regimen-related toxicity (RRT) and early posttransplant survival. Nineteen patients developed life-threatening (grade 3) or fatal (grade 4) RRT in one or more organs. Grade 3 or 4 RRT was more common in patients with advanced disease versus those transplanted earlier in their course (P = .008), and was more common in patients with advanced disease conditioned with cytarabine (Ara-C)/total body irradiation (TBI) versus those prepared with cyclophosphamide (CY)/TBI (P = .033). There was no significant difference in the incidence of grade 3 or 4 toxicity in autologous, histocompatibility locus antigen (HLA)-identical, or HLA-mismatched marrow recipients. Grade 3 or 4 RRT tended to be more common and 100-day survival worse in patients with a Karnofsky performance status of less than 90 (P = .063 and .0002, respectively). Patients receiving 20 Gy or more of mediastinal irradiation before coming to transplant had more idiopathic or cytomegalovirus (CMV) interstitial pneumonitis than those who received less than 20 Gy (30% v 9%, P = .027). The probability of survival decreased with the number of organs in which toxicity was observed (P = .0001). Severe or fatal toxicities directly related to the preparative regimen are a significant problem in the treatment of patients with advanced malignant lymphoma and can be reduced by carrying out transplantation earlier in the course of the disease.
Increased health service use for allergy in adults: Northumbrian hospital episodes, 2010–2015
Authors: I. Shiue
Journal: Allergy (2015)

Little is known on the health service use for allergy. Therefore, the aim of this study was to investigate the hospital episode rates in allergy by sex and across age groups in order to understand whether and how the health service use for allergy might have changed in recent years in north-east of England.Hospital episode data in mid-2010 to mid-2015 covering five full calendar years were extracted from Northumbria Healthcare NHS Foundation Trust, which is serving nearly half of a million population and free from central government control. Hospital episode rates were calculated from all admissions divided by annual and area-specific population size for each sex and age group, presented with per 100 000 person-years using Microsoft Excel.Health service use for allergy in adults for both men and women has increased, with large increases in young adults aged 40-49 (both male and female), 50-59 (female) and 60-69 (male). In children, there were decreases in those aged 0-9, but increases in those aged 10-19. Emergency admissions due to allergy were only minimal. Higher admissions were observed in spring and autumn than in summer and winter.Allergy admissions have increased in adults. For future research, local health policy could benefit from annual clinical records on health service use due to allergy. For clinical practice, in addition to increasing and improving the role of health and nursing professionals to reduce burden and rehabilitation, public awareness, attitude and knowledge should be continuously raised and improved as well.
Abstract 3093: Long Term Prognostic Value of Stress Perfusion CMR and Late Gadolinium Enhanced CMR for The Prediction of Major Adverse Cardiac Events.
Authors: Tairo Kurita, Hajime Sakuma, Katsuya Onishi, Motonori Nagata, Takeshi Takamura, Masaki Ishida, Naoki Fujimoto, Kaoru Dohi, Kan Takeda, Masaaki Ito
Journal: Circulation (2007)

Background: Combined stress myocardial perfusion (S-PERF) and late gadolinium enhanced (LGE) CMR allows for the detection of myocardial ischemia and infarction. However, prognostic values of S-PERF and LGE CMR have not been determined in a large number of patients. In this study we determined the prognostic significance of combined S-PERF and LGE CMR study. Methods: We studied 826 patients who underwent both stress-rest perfusion CMR and LGE CMR. Stress-induced ischemia on S-PERF CMR and myocardial infarction on LGE CMR were qualitatively determined. Major adverse cardiovascular event (MACE) was defined as cardiac death, non-fatal acute myocardial infarction, heart failure on admission. Patients who underwent revascularization within 2 month after CMR were excluded. Results: During a median follow-up time of 34 months (range, 2 to 96 months), event-free survival rate was 89% in S-PERF(−)/LGE(−), 64% in S-PERF(−)/LGE(+), 49% in S-PERF(+)/LGE(−), and 38% in S-PERF(+)/LGE(+) group (P&lt;0.001 between any combinations). Abnormality on S-PERT/LGE CMR was a significant negative prognostic factor of MACE with a high hazard ratio of 7.0 (95% CI 3.9–12.7, P&lt;0.001). While LGE also predicted patients outcome, its hazard ratio (1.42, 95% CI 1.22–1.67, P&lt;0.001) was lower than that by S-PERT/LGE CMR (FIgure 1 ). Normal S-PERF/LGE CMR was associated with lower event rate per year (1.6%) as compared with that by normal LGE alone (4.3%, P&lt;0.001). Conclusions: Combined S-PERF and LGE CMR can provide improved prognostic value when compared with LGE CMR alone in patients with known or suspected coronary artery disease. Patients with normal S-PERF and LGE CMR were at low risk of adverse outcome. Figure 1: Kaplan- Meler survival distributions based on presence of LGE alone (left) and any abnormality on S-PER/LGE CMR (right)
Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production
Authors: Anja Brehm, Yin Liu, Afzal Sheikh, Bernadette Marrero, Ebun Omoyinmi, Qing Zhou, Gina Montealegre, Angelique Biancotto, Adam Reinhardt, Adriana Almeida de Jesus, Martin Pelletier, Wanxia L. Tsai, Elaine F. Remmers, Lela Kardava, Suvimol Hill, Hanna Kim, Helen J. Lachmann, Andre Megarbane, Jae Jin Chae, Jilian Brady, Rhina D. Castillo, Diane Brown, Angel Vera Casano, Ling Gao, Dawn Chapelle, Yan Huang, Deborah Stone, Yongqing Chen, Franziska Sotzny, Chyi-Chia Richard Lee, Daniel L. Kastner, Antonio Torrelo, Abraham Zlotogorski, Susan Moir, Massimo Gadina, Phil McCoy, Robert Wesley, Kristina Rother, Peter W. Hildebrand, Paul Brogan, Elke Krüger, Ivona Aksentijevich, Raphaela Goldbach-Mansky
Journal: Journal of Clinical Investigation (2015)

Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production.
A combination chemotherapy of carboplatin and irinotecan in elderly patients with small cell lung cancer (SCLC)
Authors: H. Okamoto, H. Kudoh, A. Nagatomo, H. Kunikane, K. Watanabe
Journal: Journal of Clinical Oncology (2004)

7212 Background: We have reported that carboplatin plus etoposide is an active and relatively nontoxic regimen in elderly patients (pts) with SCLC (J Clin Oncol 1999 17:3540). Recently, Japan Clinical Oncology Group has shown that irinotecan plus cisplatin is more effective than etoposide plus cisplatin for treating non-elderly pts with extensive disease (ED)-SCLC (N Engl J Med 2002;346:85). Therefore, we conducted a prospective feasibility study designed specifically to evaluate the efficacy of carboplatin (day 1) and irinotecan (days 1, 8, 15) with G-CSF support in elderly pts with SCLC. Methods: This trial had three carboplatin AUC and irinotecan dose levels of 4 mg/ml x min and 50 mg/m2 (level 1), 5/50 (level 2), and 5/60 (level 3). In another phase I trial of this combination for non-SCLC performed at our institution, the recommended dose was level 3 (Cancer 1998;82:2166). Because current trial included only elderly pts, the recommended dose was reduced to level 2. If pts had medical comorbidity, history of prior chemotherapy, PS of 2, or were 75 or more years old, the level administered was reduced by 1. If pts had PS of 0, the dose level was increased by 1. Cycles were repeated every four weeks and pts aged 70 years old or more with a PS of 0 to 2 were eligible. Results: Eighteen pts (Levels 1/2/3: 9/7/2) were enrolled in this study. The pts characteristics were as follows: median age, 75 years; limited disease (LD)/ED, 8/10 pts; previously untreated/treated: 9/9 pts; PS 0–1/2, 13/5 pts. Seventeen (94%) pts received two cycles or more of chemotherapy. Median actual delivery of irinotecan was 84% of projected doses. Grade 3/4 neutropenia, anemia and diarrhea occurred in 44%, 33% and 6% of pts, respectively. Other toxicities were mild and no treatment-related deaths occurred. There were two CRs and 14 PRs, for a response rate of 89%. The estimated median survival time was 12.0 months. Conclusions: This combination is a highly active and non-toxic regimen in elderly pts with SCLC and should be evaluated in future phase III trials. No significant financial relationships to disclose.
Micrometastases of Bone Marrow in Localized Prostate Cancer: Correlation With Established Risk Factors
Authors: Dorothea Weckermann, Peter Müller, Friedhelm Wawroschek, Gunnar Krawczak, Gert Riethmüller, Günter Schlimok
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The presence of cytokeratin 18–positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer. PATIENTS AND METHODS: Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis. RESULTS: In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors. CONCLUSION: We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.
Psychosocial Characteristics of Individuals With Non–Stage IV Melanoma
Authors: Peter C. Trask, Amber G. Paterson, Satoru Hayasaka, Rodney L. Dunn, Michelle Riba, Timothy Johnson
Journal: Journal of Clinical Oncology (2001)

Melanoma is the fastest growing solid tumor among men and women and accounts for 79% of skin cancer-related deaths. Research has identified that distress is frequently associated with a diagnosis of cancer and may slow treatment-seeking and recovery, increasing morbidity and even mortality through faster disease course. Given that the 5-year survival rates for individuals with melanoma are determined primarily by the depth and extent of spread, distress that interferes with seeking treatment has the potential to be life-threatening.The current study was designed to identify levels of distress present in individuals seeking treatment at a large, Midwestern, multidisciplinary melanoma clinic. It also focused on determining the quality of life, level of anxiety, and coping strategies used by individuals with melanoma before treatment. Given that the course of treatment and outcome for patients with stage IV disease is vastly different from that of patients with stages I to III disease, they were excluded from the study.Results indicated that most individuals who are presenting to a melanoma clinic do not report a clinically significant level of distress. However, there is some variability in this, with 29% of patients reporting moderate to high levels of distress. Moreover, analyses suggest that distressed individuals are more likely to use maladaptive coping strategies, such as escape-avoidance coping, and to have poorer quality of life.Although most individuals do not present with significant levels of distress, a significant minority are distressed and rely more heavily on coping strategies that do not benefit them. Such individuals would likely benefit most from psychological intervention.
Tobacco smoking and cardiovascular parameters
Authors: Tatiana Levina, Julia Krasnova, Alexander Dzizinskii
Journal: European Respiratory Journal (2011)

The aim: To study the influence of tobacco smoking on cardiovascular parameters.   Materials and methods:  100 smokers were examined (index of smoking≥5 packs/years). The mean age was 42,7±7,57years. The acute tests were carried out: the 1st one was smoking 1 cigarette, then after 24 hours the 2nd test was smoking 2 cigarettes. The parameters were studied before and after smoking 1 and 2 cigarettes: diameter of a humeral artery, pulsioxymetry, Holter monitoring ECG.   Results:  Diameter of a humeral artery in ten minutes after smoking 1 and 2 cigarettes decreased by 5,48% (2,4-8,9) and 6,89% (2,96-10,23), accordingly, p>0,05. Diameter of a humeral artery in fifteen minutes after smoking 1 and 2 cigarettes decreased by 6,25% (3,7-9,9) and 8,29% (3,42-12,58), accordingly, p>0,05. Diameter of a humeral artery in twenty minutes after smoking 1 and 2 cigarettes decreased by 6,71% (3,79-10,9) and 8,6% (5,11-12,78), accordingly, p   Conclusion:  Tobacco smoking can cause significant changes of cardiovascular parameters.The smoking of 2 cigarettes gives more distinctive changes in cardiovascular parameters.
Extracontractual referrals
Authors: S J Cornell
Journal: BMJ (1995)

who suffered all of these emotions-and more-for three centuries, as well as the ravages of poor or no education, housing, nutrition, and health care?Overwhelmingly, black people supported sanctions.Contrary to the rather silly editorial that Craw- shaw quotes from the Cape Times, "the campaign" (for sanctions) did not play into the hands of the "destructive right-wing," which is now an irrelevant force in South Africa.Rather, it led to the emergence of the remarkable Nelson Mandela and his government of reconciliation and the appointment of the able new minister for health, Dr Nkosazana Zuma.Like so many academics and professionals who were opposed to apartheid, she was forced into exile and suffered far more than mere "damaged self esteem."Having publicly supported sanctions for over 30 years (even while I was an academic in South Africa), I now take the opposite view and urge the strongest possible links-academic or other-with the country to help repair the damage of the past and build the sort of country free of prejudice that most South Africans wish to see.