tbuckley/cabot-search huggingface dataset:
Abstract 2121: High-resolution melting for detection of KRAS and EGFR mutations in tumors of the alimentary system
Authors: Mei Li, Lina Liu, Luming Zhou, Zhimin Liu, Lu Feng, Qiuping Zhang, Zhaohui Wang, Shen Lu
Journal: Cancer Research (2010)

Abstract The EGFR/Ras/Raf/MAPK pathway is one of the most important signal transduction pathways in cells. Dysregulation of this pathway is a common event in many cancers, including cancers of the alimentary system. EGFR and KRAS are two common genes in which mutations caused abnormal activation of the pathway. EGFR mutations are closely associated with a favorable response to treatment with tyrosine kinase inhibitors. KRAS mutations are associated with unresponsiveness to EGFR inhibitors. EGFR and KRAS mutation detection is important for carcinogenesis research and clinical therapy. Tumor tissue samples included 13 esophagus cancer, 52 gastric cancer and 67 colon cancer from a Chinese population. These were obtained from Dalian Medical University collection. High resolution melting (on a LightScanner™) was used to scan the mutations of KRAS exon 2, EGFR exon 19 and exon 21. All mutations detected by HRM were sequenced to identify the genotype. We found KRAS mutations in 5 (9.6%) patients with gastric cancer (2 with G12D; 1 with G12V; 2 with G13D) and 19 (28.4%) patients with colon cancers (11 with G12D, 3 with G12V, 4 with G13D; 1 with G13V). No KRAS mutations were found in esophagus cancer patients. The frequency of KRAS mutations in colon cancer was significantly higher than those in esophagus and gastric cancer (P&amp;lt;0.01). In 19 colon cancer patients with KRAS mutations, there were 6 (20.7%, 6/29) cases in the right colon (ascending colon and proximal 2/3 transverse colon) and 13 (34.2%, 13/38) cases in the left colon (distal 1/3 transverse colon, sigmoid colon and rectum). There is no significant difference in KRAS mutation frequencies between the right and the left colon. KRAS mutations were not associated with genders, ages, the invasive depth, lymph node metastasis and histopathological types in gastric and colon cancers. There were no EGFR exon 19 mutations found in any cases. EGFR exon 21 mutations were found in 2 gastric cancer patients (1 with L858R; 1 with G863D). In cancers of the alimentary system, KRAS mutations were more common than EGFR mutations, and KRAS mutations could be associated with the original tissues in the embryonic development. Namely, KRAS mutations were more common in cancers of organs from the midgut and hintgut than of those from the foregut, while EGFR mutations were all found in organs from the foregut. High resolution melting was a valuable method both in research and clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2121.
RISK STRATIFICATION OF PATIENTS UNDERGOING MAJOR NON-CARDIAC SURGERY AND IMPLICATIONS OF PREOPERATIVE ECHOCARDIOGRAPHY
Authors: Yang Shi, Rachel Pedersen, Matthew W. Rappelt, Robyn Shearer, Nasir Sulemanjee, Dianne Zwicke, Thomas Hastings, Cheema Omar, Vinay Thohan
Journal: Journal of the American College of Cardiology (2016)
Traffic Radar and Cancer: Smoking Gun?
Authors: N. Volkers
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Traffic Radar and Cancer: Smoking Gun? Get access Nancy Volkers Nancy Volkers Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 18, 18 September 1991, Page 1290, https://doi.org/10.1093/jnci/83.18.1290 Published: 18 September 1991
Development of a family medicine specialty training programme in Lesotho
Authors: Sebaka Malope, Elizabeth Nkholongo, Kristin Shaw, Brian Penti, Rudolf Schumacher, Jeffrey Markuns, Brian Jack
Journal: The Lancet Global Health (2016)

Background Lesotho has a severe shortage of human resources for health. Many young and talented Basotho leave the country each year to attend medical school, but usually they do not return, in part because of the lack of opportunity for continuing education and specialty training in Lesotho. Here, we describe a family medicine specialty training programme (FMSTP), which aims not only to recruit Basotho physicians back to Lesotho but also increase the number of well trained physicians in Lesotho who have the knowledge, skills and commitment to meet the health needs of the people of Lesotho, especially in district hospitals.
Reply to Hagiwara
Authors: T. Iwasa, K. Nakamura, H. Ogino, Y. Iboshi, A. Aso, E. Ihara, R. Takayanagi
Journal: Endoscopy (2011)

We sincerely thank Dr. Hagiwara for his letter regarding our article on multiple intestinal ulcers during tocilizumab therapy for rheumatoid arthritis [1]. Dr. Hagiwara described his experience of an adverse event of bleeding from multiple colonic diverticula after tocilizumab administration and re-administration. Nishimoto et al. reported that the adverse effects of tocilizumab included gastrointestinal perforation, apparently related to diverticulitis [2]. As we pointed out [1], interleukin-6 plays an important role not only in the inflammatory process, but also in intestinal tissue repair. It is therefore possible that tocilizumab administration could exacerbate diverticulitis, leading to subsequent perforation or bleeding. In our case, as we suggested previously [1], tocilizumab might have delayed wound healing and thus augmented mucosal injury due to other factors, rather than acting as a direct cause of intestinal ulcers. The possible causes of intestinal mucosal damage in our patient included infection and nonsteroidal anti-inflammatory drugs (NSAIDs). As we discussed [1], infection represented a possible cause of ulcers because of the immunocompromised nature of the patient. Celecoxib, which is a cyclooxygenase-2-selective inhibitor with a lower risk of gastrointestinal mucosal damage than classical NSAIDs, was given to relieve arthralgia. However, Chang et al. reported that even celecoxib could increase the risk of lower gastrointestinal adverse events [3]. It is therefore likely that erosions or small ulcers initially developed as a result of infection or celecoxib treatment, and that tocilizumab subsequently suppressed mucosal healing, allowing their deterioration into intestinal ulcers. This suggests that attention should be paid to pre-existing gastrointestinal injuries before administering tocilizumab therapy, to reduce the risk of adverse gastrointestinal events. We therefore recommend the use of esophagogastroduodenoscopy, colonoscopy, or capsule endoscopy before starting tocilizumab therapy.
Abstract 2131: Accurate quantitation of absolute allelic copy-numbers in primary solid tumor samples from SNP-array / WGS data reveals patterns of tumor progression
Authors: Scott L. Carter, Gad Getz, Matthew L. Meyerson
Journal: Cancer Research (2010)

Abstract Genomic imbalances are a hallmark of cancer cells. Genomic regions recurrently gained or lost in many cancer samples often harbor oncogenes or tumor suppressors, making whole-genome characterization of copy-number a widely adopted strategy for the study of cancer In practice, copy-number analysis is typically performed using techniques such as array-CGH, SNP-array, or whole genome sequencing (WGS) analysis. Because a fixed quantity of DNA is extracted from a tumor sample for each of these methods, the concentration of each genomic locus is dependant on both the fraction of tumor cells and the ploidy (DNA mass) of each tumor cell. Because these quantities are generally unknown, downstream analysis of copy-number changes has been limited to consideration of relative gains/losses. Here we describe a recently developed computational method capable of accurately inferring the tumor purity, ploidy, and genome-wide absolute allelic copy-numbers from data obtained by either SNP-array (several platforms are supported), or WGS. Validation data comprised of tumor-normal cell-line mixing experiments verify the accuracy of the method. Application of these methods to large tumor-cohorts allowed for systematic re-assessment of homozygous deletion and LOH in heavily contaminated samples. These results allow for the assessment of preferential allelic deletion or amplification in genomic regions of recurrent copy loss or gain, respectively. Our data suggest that the distribution of tumor-ploidy is bi-modal for many common epithelial tumor types, with a hypo-diploid subset and a second subset of samples with ploidy ranging from three to five [haploid genomes]. The observed patterns of allelic copy-number are consistent with a model of tumor progression by which high-ploidy samples arose via whole-genome doubling from an intermediate hypo-diploid state. These analyses allow us to define characteristic “early” genomic events in several tumor types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2131.
Recent advances: Cardiopulmonary resuscitation
Authors: K. A Ballew
Journal: BMJ (1997)

Coronary artery disease is the leading cause of death in most developed countries.In the United States alone, 500 000 deaths a year are caused by coronary artery disease, over half of which are due to sudden cardiac arrest. 1 Often cardiac arrest is the initial manifestation of coronary artery disease, so many of these patients if successfully resuscitated could have years of productive life remaining.Improvements in cardiopulmonary resuscitation therefore could have an appreciable impact on total mortality. Recent advances in cardiopulmonary resuscitationSudden cardiac arrest remains a major cause of death in developing countries Despite years of experience with cardiopulmonary resuscitation, survival after cardiac arrest continues to be quite low Automatic external defibrillators and bystander cardiopulmonary resuscitation improve survival after sudden cardiac arrest Doctors should identify and counsel those patients who are not candidates for cardiopulmonary resuscitation
SAT0245 Evaluation of Lesions in the Zygapophyseal Joints and their Correlation with Functional Changes in Patients with Ankylosing Spondylitis
Authors: S. Kovalenko, G. Protsenko, V. Kachur, I. Kateryna
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondyloarthritis (AS) is a chronic inflammatory rheumatic disease. Lesion of zygapophysial joints is characterized by more unfavorable course of disease. <h3>Objectives</h3> To estimate the lesion frequency of the zygapophysial joints by MRI and its impact on vertebral function in patients with AS. <h3>Methods</h3> The study involved 53 people (males) with AS and disease duration ≤ 10 years. The patients were divided into two groups: Group I – patients without lesion of zygapophysial joint but have syndesmophytis (18 people), Group II – patients with lesion of zygapophysial joint (35 people). All evaluation parameters: 10-point assessment of mobility of the spine in the cervical, thoracic, lumbar parts. <h3>Results</h3> Zygapophysial joint lesion has a high prevalence at onset disease (61,40%) and precedes, in most cases, by lesions of the vertebral body and ligaments. Involvement of that kind met mostly in patients with peripheral form of the disease: 25 patients (71.42%), especially if the peripheral joints were affected at onset disease. Spinal mobility's indicants in patients without zygapophysial joint lesions but with the presence of syndesmophyte: neck rotation 1.94 ± 0.70 points, chest excursion 4.32 ± 0.57 cm, lateral flexion 2.88 ± 0.85 points, modified Schober test 5.33 ± 0.83 points. Spinal mobility's indicants in patients with zygapophysial joint lesions: neck rotation 4.57 ± 0.38 points, chest excursion 2.79 ± 0.27 cm, lateral flexion 5.22 ± 0.41 points, modified Schober test 7.87 ± 0.35 points. We also notified the correlation between the quantity of affected joints and intensity of functional changes in spine mobility. <h3>Conclusions</h3> We observed the correlation between severity of function changes in the cervical and lumbar spine, chest excursion and the presence of facets joints lesions. The differences between groups with and without facet joint lesions were statisticaly significant, that indicates more unfavourable prognosis for a clinical course. <h3>Disclosure of Interest</h3> None Declared
Detection of a Sinus of Valsalva Aneurysm by F-18 FDG PET/CT Imaging
Authors: Bashir Akhavan Tafti, Wisam Shaba, Yuxin Li, Ella Yevdayev, Gholam Reza Berenji, Edwin Glass
Journal: Clinical Nuclear Medicine (2011)

An echocardiographic examination performed on a 72-year-old man for assessment of left ventricular hypertrophy revealed a right atrial mass, approximately 4 cm in size, attached to the interatrial septum. Given his history of leiomyosarcoma with vascular invasion, the patient was referred for PET/CT to assess the possibility of metastatic involvement. The results suggested an aneurysmal mass of the aortic noncoronary cusp consistent with a sinus of Valsalva aneurysm. A subsequent CT angiogram and surgery confirmed the diagnosis. To the best of our knowledge, this is the first reported case of a sinus of Valsalva aneurysm detected in PET/CT images.
Silent Ischemia as a Marker for Early Unfavorable Outcomes in Patients with Unstable Angina
Authors: Sidney O. Gottlieb, Myron L. Weisfeldt, Pamela Ouyang, E. David Mellits, Gary Gerstenblith
Journal: New England Journal of Medicine (1986)

We examined the prevalence and prognostic importance of silent myocardial ischemia detected by continuous electrocardiographic monitoring in 70 patients with unstable angina. All the patients received intensive medical treatment with nitrates, beta-blockers, and calcium-channel blockers. Continuous electrocardiographic recordings were made during the first two days in the coronary care unit to quantify the frequency and duration of asymptomatic ischémie episodes, defined as a transient ST-segment shift of 1 mm or more. Thirty-seven patients (Group 1) had at least one episode of silent ischemia, and the other 33 patients had no silent ischemia (Group 2). Over the subsequent month, myocardial infarction occurred in 6 patients in Group 1 and in only 1 in Group 2 (P<0.01); bypass surgery or angioplasty was required for recurrent symptomatic angina in 10 patients in Group 1 and only 3 in Group 2 (P = 0.02). Survival-curve analysis demonstrated that silent ischemia was associated with these outcomes (P<0.002), and multivariate analysis showed that silent ischemia was the best predictor of these outcomes among the 15 variables tested (P<0.002). Patients in Group 1 with 60 minutes or more of silent ischemia per 24 hours had a worse prognosis than those with under 60 minutes per 24 hours (P = 0.04). Silent ischemia occurred in more than 50 percent of our patients with unstable angina, despite intensive medical therapy, and it identified a subset who were at high risk for early unfavorable outcomes. (N Engl J Med 1986; 314:1214–9.)
The Elimination of Indigenous Measles, Mumps, and Rubella from Finland by a 12-Year, Two-Dose Vaccination Program
Authors: Heikki Peltola, Olli P. Heinonen, Martti Valle, Mikko Paunio, Martti Virtanen, Viena Karanko, Kari Cantell
Journal: New England Journal of Medicine (1994)

In the 1970s measles, mumps, and rubella were rampant in Finland, and rates of immunization were inadequate. In 1982 a comprehensive national vaccination program began in which two doses of a combined live-virus vaccine were used.Public health nurses at 1036 child health centers administered the vaccine to children at 14 to 18 months of age and again at 6 years, and also to selected groups of older children and young adults. Vaccination was voluntary and free of charge. In follow-up studies, we focused on rates of vaccination, reasons for noncompliance, adverse reactions, immunogenicity, persistence of antibody, and incidence of the three diseases. Since 1987, paired serum samples have been collected from all patients with suspected cases of measles, mumps, or rubella.Over a period of 12 years, 1.5 million of the 5 million people in Finland were vaccinated. Coverage now exceeds 95 percent. The vaccine was efficient and safe, even in those with a history of severe allergy. No deaths or persistent sequelae were attributable to vaccination. The most frequent complication requiring hospitalization was acute thrombocytopenic purpura, which occurred at a rate of 3.3 per 100,000 vaccinated persons. The 99 percent decrease in the incidence of the three diseases was accompanied by an increasing rate of false positive clinical diagnoses. In 655 vaccinated patients with clinically diagnosed disease, serologic studies confirmed the presence of measles in only 0.8 percent, mumps in 2.0 percent, and rubella in 1.2 percent. The few localized outbreaks were confined to patients in the partially vaccinated age groups. There are now fewer than 30 sporadic cases of each of the three diseases per year, and those are probably imported.Over a 12-year period, an immunization program using two doses of combined live-virus vaccine has eliminated indigenous measles, mumps, and rubella from Finland. Serologic studies show that most reported sporadic cases are now due to other causes, but a continued high rate of vaccination coverage is essential to prevent outbreaks resulting from exposure to imported disease.
Whatever Happened to Beta Carotene?
Authors: D. Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Whatever Happened to Beta Carotene? Get access David Holzman David Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 23, 6 December 1995, Pages 1739–1741, https://doi.org/10.1093/jnci/87.23.1739 Published: 06 December 1995
Abstract LB-119: Nucleolin promotes leukemogenesis through DNA hypermethylation.
Authors: Na Shen, Fei Yan, Jiuxia Pang, shujun Liu
Journal: Cancer Research (2013)

Abstract Nucleolin (NCL), an abundant multifunctional phosphoprotein, is upregulated in numerous cancers. While NCL overexpression is implicated in tumor growth and angiogenesis, how NCL over-function contributes to tumorigenesis is poorly understood. Aberrant activity of DNA methyltransferase (DNMT) has been well documented in cancers and higher DNMT expression predicts worse prognosis, but how DNMT gene is regulated remains elusive. Given that NCL deregulation disrupts NFκB pathway, a DNMT1 gene transactivator, we speculated that NCL might promote cancer via DNA hypermethylation. To test this, initially we statistically analyzed 5 datasets from Gene Expression Omnibus. We found that NCL expression is elevated (n=121) and positively correlated with DNMT1/3a/3b in leukemia patients (n=242), indicative of their functional interaction in leukemogenesis. When Kasumi-1 and MV4-11 cells were transfected with NCL siRNA for 48 hours, by Western blot and PCR, we observed that NCL knockdown caused DNMT downregulation. Similar results were obtained when Kasumi-1 and MV4-11 cells were exposed to 1µM or 3µM of AS1411, a quadruplex DNA aptamer binding to NCL, for 48 hours. In contrast, ectopic expression of NCL in 293T cells upregulated DNMT, arguing for the positive role of NCL in DNMT transcription. Mechanistically, NCL-driven DNMT upregulation occurred via NFκB signaling, as NCL dysfunction (by siRNA and AS1411) dephosphorylated NFκBp65 (Ser536), and siRNA-mediated NFκB depletion abolished its phosphorylation leading to DNMT suppression. We then extracted genomic DNA from the above treated cells and subjected to Dotblot using 5mC antibody. We evidenced that NCL inactivation induced global DNA hypomethylation, whereas NCL overexpression resulted in DNA hypermethylation. Functionally, NCL inhibition by siRNA and AS1411 activated caspase-3 and caspase-8 and significantly abrogated leukemia cell clonogenic potential. Further, when MV4-11 cells were transfected with NCL siRNA, at 6 hours after transfection when the cells were not apoptotic, 2X106 cells were injected subcutaneously into nude mice for tumorigenesis (n=6). Compared to scramble control, we found that NCL knockdown dramatically decreased tumor volume and weight. H&amp;E and IHC staining by Ki-67 or 5mC indicated the excessive reduction of tumor-forming rate and the significant decrease of DNA methylation. Thus, our collective findings highlight the interactive features between DNMT machinery and NCL oncogenic pathway providing a rationale for targeting NCL as a general approach to treat cancers unresponsive to current DNA methylation inhibitor therapy. Citation Format: Na Shen, Fei Yan, Jiuxia Pang, shujun Liu. Nucleolin promotes leukemogenesis through DNA hypermethylation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-119. doi:10.1158/1538-7445.AM2013-LB-119