tbuckley/cabot-search huggingface dataset:
Abstract A67: Methylation of ESR1 and 14-3-3 sigma promoter in serum as possible biomarkers for screening and diagnosis for breast cancer
Authors: Joaquina Martinez-Galan, Blanca Torres-Torres, Juan Ramón Delgado
Journal: Cancer Research (2013)

Abstract Background: To investigate the association between gene hypermethylation and the major clinico-pathological features of breast cancer, including diagnosis and treatment response. Material and Methods: 107 women with breast cancer and 108 control subjects were recruited. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the utility of circulating DNA with CpG island hypermethylation of APC, RAR-β, E-Cadherin, ESR1 and 14-3-3 sigma; gene promoter regions as breast cancer biomarkers. Sera were collected in 107 operable breast cancer patients (pts) previously surgery and in 60 of those pts after treatment. Respect controls, 34 had benign breast disease and 74 with no evidence of breast disease. Results: We found significant differences between breast cancer patients and healthy controls in relative serum levels of methylated gene promoters ESR1 (p = 0.0112) and 14-3-3sigma (p=0.0047). We observed that hypermethylation of these combined two genes differentiated between breast cancer patients and healthy controls (p &amp;lt;0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94 %). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p = 0.0179); and presence of methylated 14-3-3-sigma was associated with T3-4 stage (OMS) (p&amp;lt; 0.05) and nodal positive status (p&amp;lt; 0.05). We observed lower methylated ERS1 or 14-3-3-sigma values after surgery, respect pretreatment levels, but without an overall statistically significant difference. With a median follow up of 6 years, we found that patients with a significant decrease of sera methylated levels of both genes after surgery had better time to progression an overall survival respect patients without this observation. Conclusions: this panel of genes detected in ductal lavage and blood specimens could be useful as markers for early detection of breast carcinoma. These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer risk assessment. Note: This abstract was not presented at the conference. Citation Format: Joaquina Martinez-Galan, Blanca Torres-Torres, Juan Ramón Delgado. Methylation of ESR1 and 14-3-3 sigma promoter in serum as possible biomarkers for screening and diagnosis for breast cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A67.
Effects of Cigarette Smoking on Endurance Performance
Authors: Kenneth H. Cooper
Journal: JAMA (1968)

By means of a 12-minute field test, the effect of cigarette smoking on endurance performance was measured in 419 airmen before and after six weeks of basic training. In 47 airmen, cardiopulmonary indexes also were obtained during maximal treadmill performance. Field testing showed that endurance performance was inversely related to the number of cigarettes smoked daily and the duration of smoking. The training response also was impaired significantly in the smokers. During treadmill studies, smokers had a decrease in respiratory minute volume and a lower oxygen consumption at equivalent heart rates than nonsmokers. Further statistical studies demonstrated not only the independent effect of smoking, but also the effect of prior athletic history and physical characteristics on endurance performance. The latter effects become less significant as physical training progressed.
Abstract 3109: ALK as a valid therapeutic target for the treatment of rhabdomyosarcoma
Authors: Monika Wierdl, Lyudmila Tsurkan, Viktor Tollemar, Lying Chi, Elizabeth Stewart, Michael A. Dyer, Philip M. Potter
Journal: Cancer Research (2014)

Abstract Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor tyrosine kinase, a member of the insulin receptor family, with a tightly controlled expression pattern. Deregulated ALK expression has been linked to the development of several types of cancers. Typically, chromosomal translocations involving ALK generate constitutively expressed chimeric oncoproteins, such as NPM-ALK in anaplastic large cell lymphoma and EML4-ALK in non-small cell lung carcinoma. However, activating mutations in ALK, and increased copy number that result in aberrant gene expression, have also been observed in neuroblastoma and colorectal cancers. Based on the above observations, several small molecule ALK inhibitors have been developed and are in clinical trials for a variety of tumors expressing this kinase. This has resulted in the use of crizotinib for the treatment of EML4-ALK + lung cancers. Recently several large scale immunohistochemistry and genome sequencing studies of pediatric rhabdomyosarcoma (RMS) revealed aberrant ALK expression. It was found that ALK mRNA expression was significantly different in alveolar (ARMS) and embryonic RMS (ERMS), the two major histological subtypes in children. Thus, ALK expression might play a role in tumorigenesis for this disease, and this kinase may represent a valid therapeutic target for the treatment of RMS. To answer this question we analyzed ALK expression in a large panel of RMS cell lines, and pediatric tumor samples by quantitative PCR and immunoblotting. We also compared the sensitivity of these cells to a series of ALK inhibitors. Our results indicate that the majority of ARMS cell lines demonstrated significantly higher ALK mRNA expression as compared to ERMS, and to normal human myoblast control cells. This was confirmed by western analysis. Growth inhibition assays confirmed that all RMS lines were more sensitive to crizotinib and LDK-378 than control lines, consistent with the hypothesis that ALK is a driver of cell growth in these tumors. Based on our in vitro analysis, we suggest that ALK inhibition may represent an effective therapeutic modality for the treatment of ALK+ RMS. Preclinical studies to confirm or disprove this hypothesis are currently underway. Supported by St. Jude Children's Research Hospital and by the American Lebanese Syrian Associated Charities Citation Format: Monika Wierdl, Lyudmila Tsurkan, Viktor Tollemar, Lying Chi, Elizabeth Stewart, Michael A. Dyer, Philip M. Potter. ALK as a valid therapeutic target for the treatment of rhabdomyosarcoma. [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 3109. doi:10.1158/1538-7445.AM2014-3109
Effects of hemodialysis dose and membrane flux on health-related quality of life in the HEMO Study
Authors: Mark Unruh, Robert Benz, Tom Greene, Guofen Yan, Srinivasan Beddhu, Maria Devita, Johanna T. Dwyer, Paul L. Kimmel, John W. Kusek, Alice Martin, Josephine Rehm-Mcgillicuddy, Brendan P. Teehan, Klemens B. Meyer
Journal: Kidney International (2004)
Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment
Authors: M Ostergaard
Journal: Annals of the Rheumatic Diseases (2005)

By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression.100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36.MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression.Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.
Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections
Authors: Mark S. Sulkowski, David L. Thomas, Shruti H. Mehta, Richard E. Chaisson, Richard D. Moore
Journal: Hepatology (2002)

Hepatologists are frequently asked to evaluate human immunodeficiency virus (HIV)-infected patients with abnormal liver enzymes and to assess the causal role of medications, such as antiretroviral drugs. Recently, the use of HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine (NVP) and efavirenz (EFV), has been associated with severe hepatic injury. We prospectively studied the incidence of severe hepatotoxicity (grade 3 or 4 change in alanine or aspartate transaminase levels) among 568 patients receiving NNRTI-containing antiretroviral therapy, including 312 and 256 patients prescribed EFV and NVP, respectively. Hepatitis C virus (HCV) and hepatitis B virus (HBV) were detected in 43% and 7.7% of patients, respectively. Severe hepatotoxicity was observed in 15.6% of patients prescribed NVP and 8.0% of those prescribed EFV, but only 32% of NVP and 50% of EFV-associated episodes were detected during the first 12-weeks of therapy. The risk was significantly greater among persons with chronic viral hepatitis (69% of cases) and those prescribed concurrent protease inhibitors (PIs) (82% of cases). Nonetheless, 84% of patients with chronic HCV or HBV did not experience severe hepatotoxicity. Severe hepatotoxicity occurs throughout the course of NNRTI therapy and is more common among patients prescribed nevirapine, those coinfected with HCV or HBV, and those coadministered protease inhibitors.
Cancer of the gastrointestinal tract. Endoscopic diagnosis
Authors: J. F. Morrissey
Journal: JAMA (1973)

In the past years, the endoscopist was limited to the use of rigid or flexi-rigid open-tipped esophagoscopes; the information that he was able to add in the diagnosis of esophageal malignancy to what had been obtained from a barium meal esophagram and a lavage cytology was often disappointingly small. Angulation and fixation of the esophagus often prevented visualization of the lesion; few endoscopists were able to obtain biopsies showing malignancy from more than 50% of tumors. The introduction of flexible forwardviewing fiberoptic endoscopes, which were 65 cm to 77 cm long, greatly improved this situation.<sup>36-38</sup>These instruments had short controllable tips that permitted easy passage through the esophagus in all patients except those with very tight strictures. The automatic controls for air, water, and suction provided a clear field in the presence of food, mucus, or even active bleeding. Adequate light for both visualization and photography were provided by
PAROXYSMAL TACHYCARDIA: ITS RELATION TO EXOPHTHALMIC GOITER.
Authors: CARL C. WARDEN
Journal: JAMA (1906)

It is my wish to emphasize the relationship apparently existing between certain cases of paroxysmal tachycardia and exophthalmic goiter, and to suggest that a more thorough examination of such cases may serve to trace the connection in a considerable proportion of instances. The more I see of this symptomatic disturbance, the less inclined am I to regard it as a definite entity or deserving of special caption in the category of disease. A superficial survey of the literature shows some 160 references to the subject, and as yet there has been no opportunity to observe what proportion of the cases are regarded by their reporters to have been due to exophthalmic goiter, though it is apparent that the percentage is small. It is hoped that a thorough resumé of the subject may be embodied in a future note. The present communication is actuated by two recent cases in my practice,
Abstract 3231: In vitro cross species metabolism of a novel RAF kinase inhibitor phosphate prodrug, ARQ 736
Authors: Terence Hall, Karen Bresciano, Laurie Volak, Yunxia Wang, Caiyun Zhong, Yanbin Liu, Jean-Marc Lapierre, Ronald E. Savage, Thomas C.K. Chan
Journal: Cancer Research (2011)

Abstract ARQ 736 is a highly-soluble phosphate prodrug that readily undergoes conversion to ARQ 680 in the presence of phosphatases. The active drug, ARQ 680, is a pan-RAF inhibitor that is effective, both in vitro and in vivo, in inhibiting proliferation of cancer cell lines expressing mutant-BRAF (V600E). During preclinical development, the metabolic fate of ARQ 736 and ARQ 680 was evaluated in human, rat, and dog in vitro systems. Based on the data generated, metabolic pathways were proposed for ARQ 736 and ARQ 680. Cross-species metabolic stability studies were conducted in microsomes and hepatocytes. CYP450 reaction phenotyping using 6 recombinant CYP isozymes was conducted to identify the CYP isozyme(s) responsible for the phase one metabolism of ARQ 736 and ARQ 680. ARQ 736 and ARQ 680 were incubated in hepatocytes and liver fractions to evaluate the phase one and phase two metabolites produced in humans rats, and dogs. Additional studies in microsomes and hepatocytes were conducted to evaluate the potential for ARQ 736 or ARQ 680 to inhibit or induce various CYP450 isozymes. Cross-species NADPH-dependent metabolism studies revealed that ARQ 736 and 680 were highly stable in, rat, dog, and human liver microsomes with half-life values &amp;gt;30 min. CYP450 reaction phenotyping indicated that CYP3A4 is the predominant CYP450 isozyme responsible for phase one metabolism of ARQ 736 and 680. Detailed metabolite ID work in hepatocytes identified multiple phase one and two metabolites as a result of oxidations, demethylation and glucuronidation. Metabolic pathways appeared to be similar across all species tested. In conclusion, this research is the first characterization of the metabolism of ARQ 736, a novel pan-RAF inhibitor currently being tested in phase one clinical trial in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3231. doi:10.1158/1538-7445.AM2011-3231
Margaret Wilson (née Fyfe)
Authors: Roy O Walker, Janie M Wilson
Journal: BMJ (2004)

Psychiatrist and pioneer of the death-and-dying movementIn her groundbreaking bestseller On Death and Dying, Elisabeth Kübler-Ross overturned how physicians treat dying patients.When the book was published in 1969, death was a taboo subject and discussing it was considered morbid.Patients died alone in hospitals; physicians ignored them; and adequate pain medication was underused.The book brought these practices to the fore-and pressed for more humane treatment of the dying.The book rocked the medical profession-and at the same time also resulted in a public outcry for compassionate care of the dying.On Death and Dying is a classic work and is still in print around the world today.Kübler-Ross's work stemmed from the realisation that in her native Switzerland, death, like birth, was considered a normal part of the life cycle.In Switzerland people died at home surrounded by family and friends-and they were comfortable until the end of their lives.In contrast in the United States and other countries that placed a premium on high tech medicine, patients lay by the wayside.It was a practice she deplored.A hallmark of Kübler-Ross's work was her emphasis on communication.She stressed that patients truly wanted to review their lives, their deterioration, and imminent death.When patients and doctors could talk openly-and without fear-a good death could be achieved.In 1967 Kübler-Ross began interviewing dying patients at the University of Chicago's Billings Hospital, where she was a psychiatrist.She hoped to learn what patients were thinking as they lay dying.From her first hand research, she derived the famous five stage framework: denial, anger, bargaining, depression, and acceptance-or, as she called it, "one common denominator" of death and dying.The model outlined how patients with terminal illness grappled with their diagnosis, and their emotions along the way, right through to acceptance of their impending death.She appealed to the medical community to use it.Collin Murray Parkes, consultant psychiatrist at St Christopher's Hospice in London, credits Kübler-Ross's five stage framework and its high visibility as a driving force in stimulating research and changing
National Health Service Corps
Authors: Edward D. Martin
Journal: JAMA (1974)

To the Editor.—  As director of the  Health Service Corps, I agree with the point made by Pollner and Parrish in their article National Health Service Corps and Primary Care Training (228:1405, 1974) that the Corps and primary care training programs have many common interests. This is why more than one fourth of Corps sites are already affiliated with family practice programs. In seven sites, Corps assignees are presently, or soon will be, receiving residency credit. Three sites will serve as rural model family practices separated from training centers by 40 to 50 miles or more.  A larger number of affiliations could have been completed except for the fact that most of the training programs are urban-based and are not located in areas of critical need and, therefore, are not available for affiliation under current circumstances. Ultimately, it is our goal to have every site affiliated with a primary
Involvement of the vascular endothelial growth factor receptor-1 in murine hepatocellular carcinoma development
Authors: Hitoshi Yoshiji, Shigeki Kuriyama, Junichi Yoshii, Yasuhide Ikenaka, Ryuichi Noguchi, Koji Yanase, Tadashi Namisaki, Mitsuteru Kitade, Masaharu Yamazaki, Hirohisa Tsujinoue, Tsutomu Masaki, Hiroshi Fukui
Journal: Journal of Hepatology (2004)
Chemical Enhancers of Cytokine Signaling that Suppress Microfilament Turnover and Tumor Cell Growth
Authors: Hyun-Joo Park, Emily Partridge, Pam Cheung, Judy Pawling, Rob Donovan, Jeffrey L. Wrana, James W. Dennis
Journal: Cancer Research (2006)

The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell proliferation, morphogenesis, and specialized cell functions in metazoans. Herein, we screened a compound library for modifiers of TGF-beta signaling in NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear translocation. We identified five enhancers of TGF-beta signaling that share a core structure of diethyl 2-(anilinomethylene)malonate (DAM), and D(50) values of 1 to 4 micromol/L. Taking advantage of the Mgat5 mutant phenotype of accelerated receptor loss to endocytosis, we determined that DAM-1976 restored the sensitivity of Mgat5(-/-) carcinoma cells to both TGF-beta and epidermal growth factor (EGF). In Mgat5 mutant and wild-type carcinoma cells, DAM-1976 enhanced and prolonged TGF-beta- and EGF-dependent Smad2/3 and Erk activation, respectively. DAM-1976 reduced ligand-dependent EGF receptor endocytosis, actin microfilament turnover, and cell spreading, suggesting that the compound attenuates vesicular trafficking. Hyperactivation of intracellular signaling has the potential to suppress tumor cell growth and, in this regard, DAM-1976 represents a new pharmacophore that increases basal activation of Smad2/3 and Erk, inhibits microfilament remodeling, and suppresses carcinoma cell growth.
Detection of Residual Lymph Node Metastases in High-Risk Papillary Thyroid Cancer Patients Receiving Adjuvant I-131 Therapy
Authors: Koichiro Kaneko, Koichiro Abe, Shingo Baba, Takuro Isoda, Hidetake Yabuuchi, Masayuki Sasaki, Masamitsu Hatakenaka, Hiroshi Honda
Journal: Clinical Nuclear Medicine (2009)

The aims of this retrospective study were to evaluate the incidence of residual lymph node (LN) metastases in high-risk papillary thyroid cancer (PTC) patients receiving adjuvant I-131 therapy, especially in those without I-131 accumulation, and to evaluate the clinical usefulness of F-18 FDG PET/CT to detect those lesions.The 37 PTC patients receiving adjuvant I-131 therapy were retrospectively evaluated. We examined the incidence of residual LN metastasis and compared the accumulation of F-18 FDG and I-131 in those lesions, and compared the serum thyroglobulin (Tg) levels between patients with and without residual LN metastases.A total of 33 lesions were diagnosed as residual LN metastases in 9 patients. FDG accumulated in all of the lesions, but 19 lesions (57.6%) of them had no I-131 accumulation. The SUVmax was significantly higher in lesions without I-131 accumulation than in lesions with I-131 accumulation (6.6 +/- 2.8 vs. 4.2 +/- 1.8; P = 0.007). The serum Tg levels were significantly higher in patients with residual LN metastases than in patients without it (709.9 +/- 1470.8 vs. 25.6 +/- 37.1 ng/mL; P = 0.005). The incidence of residual LN metastasis was significantly higher in patients with a detectable serum Tg level than in patients without it (35.0% vs. 0%, P = 0.03).These results indicate that the residual LN metastasis was relatively common in high-risk PTC patients receiving adjuvant I-131 therapy whose serum Tg levels remained detectable, and those lesions often had no I-131 accumulation. FDG-PET/CT would be recommended for PTC patients with detectable serum Tg levels to detect residual LN metastases.
BMA warns against unnecessary screening tests in private sector
Authors: Lynn Eaton
Journal: BMJ (2005)

Patients may be putting themselves at unnecessary risk—with very little benefit to their health—by opting to undergo scans and genetic tests that are offered to them as part of a screening programme by private sector healthcare organisations.

That is the warning of a briefing paper by the BMA's Board of Science, which fears that many people are not told of the potential risks before undergoing the tests, such as whole body magnetic resonance imaging or the prostate specific antigen test for prostate cancer. It is calling on the government to address the growing problem of …