tbuckley/cabot-search huggingface dataset:
Abstract 1280: Pterostilbene exerts full protection against UVB-induced skin carcinogenesis.
Authors: Angel Ortega, Maria L. Rodriguez, Joan A. Sirerol, Ines Pulido, Daniel Crespo, Julian Carretero, Miguel A. Asensi, Salvador Mena, Jose M. Estrela
Journal: Cancer Research (2013)

Abstract Epidemiological, clinical and laboratory studies have demonstrated that solar ultraviolet (UV) radiation is the main cause of nonmelanoma skin cancer (i.e., basal cell and squamous cell carcinoma) and it is also a prime factor in the etiology of cutaneous melanoma. The cancer-causing effects of solar exposure on the skin are mainly produced by UV-B radiation in the 290- to 320-nm range, the same range that produces burning in human skin (erythema), inflammation, oxidative stress, DNA damage, etc. Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of an effective protection against UV radiation. Polyphenols (PFs) are abundant in many fruits and vegetables, wine, tea, and various dietary supplements. The role of these natural molecules as potential anticarcinogens and photoprotectors has been postulated (e.g. Clifford JL &amp; DiGiovanni J. Cancer Prev Res 3: 132-5, 2010). Resveratrol (trans-3,5,4′-trihydroxystilbene; RES) is a phytoalexin present in a wide variety of plant species, where its synthesis is induced by stress conditions. The cancer chemopreventive activity of RES was first reported by Jang et al [Science 275, 218 - 220 (1997)] in a model of skin carcinogenesis where topic administration of this polyphenol inhibited multistage mouse skin carcinogenesis. Equally promising action is exerted by resveratrol analogues, mainly pterostilbene (3,5-dimethoxy-4′-hydroxy-transstilbene: PTER), which shows a higher half-life and more potent anticancer effects in vivo than RES. The long-term UV-B administration (180 mJ/cm2; 3 doses/week; for a total of 30 weeks) reproduces, in an animal model, which are the consequences in humans of receiving chronic UV-B radiations. We observed that pretreatment of the skin with PTER prevented UV-B-induced skin tumorigenesis (∼90 % of tumor free-mice at the end of treatment, n=20; P&amp;lt;0.01). Our aim was to study the key molecular mechanisms involved in this strong anticancer effect elicited by PTER. Our results indicate that PTER efficiently avoid skin carcinogenesis induced by solar radiation by decreasing DNA mutagenesis, and protein and lipid oxidation. Citation Format: Angel Ortega, Maria L. Rodriguez, Joan A. Sirerol, Ines Pulido, Daniel Crespo, Julian Carretero, Miguel A. Asensi, Salvador Mena, Jose M. Estrela. Pterostilbene exerts full protection against UVB-induced skin carcinogenesis. [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 1280. doi:10.1158/1538-7445.AM2013-1280
Abstract 352: Preclinical evaluation of LYS6K1, a novel, highly selective, orally bioavailable inhibitor of p70 S6 kinase currently in phase I clinical trials for cancer
Authors: Sandaruwan Geeganage, Lillian L. Sams, Sajan Joseph, Leslie Brail, Tao Wang, George Rodgers, Jackie Akunda, Jianping Huang, Everett J. Perkins, Rose Ajamie
Journal: Cancer Research (2010)

Abstract PI3K/AKT/mTOR/S6K signaling pathway (AKT pathway) controls cell survival, cell-cycle progression, cell growth and metabolism through a cascade phosphorylation of a number of key substrates. This pathway is regulated by three well characterized tumor suppressors; pten, tsc2, and lkb1. Deletion of these genes results in activation of the AKT pathway and proliferative disorders. Similarly, activating mutations of the receptor tyrosine kinases or PI3 Kinase result in the activation of the pathway. Therefore, multiple nodes of the pathway have become drug targets. As part of a comprehensive drug discovery platform aimed at targeting the PI3K pathway, we have developed a potent small molecule inhibitor of p70 S6 kinase that is a downstream effector in this pathway. LYS6K1 is a potent, highly selective ATP competitive inhibitor against p70 S6 kinase with an IC50 of 0.002 uM. In vitro, LYS6K1 inhibits the phosphorylation of S6 ribosomal protein in HCT116 colon cancer cells with an IC50 of 0.2 uM and similar activity is seen in a broad range of other cell lines. In vivo, LYS6K1.tosylate demonstrates potent phospho-S6 inhibition in nude mice bearing HCT116 colon carcinoma cells, with an ED50 value of 2.2 mg/kg and a ED90 value of 10 mg/kg 4 hours after a single oral dose. In these studies, LYS6K1.tosylate did not show statistically significant elevation of phospho-AKT, in spite of potent p70 S6 kinase inhibition. Proportional dose, exposure, and pharmacodynamic relationships were observed for LYS6K1 in dose- and time- dependent studies. In vivo, LYS6K1.tosylate effectively inhibits the growth of HCT116 colon carcinoma xenografts in mice and the growth of U87MG glioblastoma tumor as a single agent at 2.5 mg/kg given twice daily. Overall, LYS6K1.tosylate has high permeability that resulted in good oral absorption and PK properties. Based on these pre-clinical observations, LYS6K1.tosylate has advanced to Phase I studies. 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 352.
High-Dose Therapy and Autologous Bone Marrow Transplantation after Failure of Conventional Chemotherapy in Adults with Intermediate-Grade or High-Grade Non-Hodgkin's Lymphoma
Authors: Thierry Philip, James O. Armitage, Gary Spitzer, Franck Chauvin, Sundar Jagannath, Jean-Yves Cahn, Philippe Colombat, Antony H. Goldstone, Norbert C. Gorin, Michel Flesh, Jean-Philippe Laporte, Dominique Maraninchi, José Pico, André Bosly, Cathy Anderson, Rik Schots, Pierre Biron, Fernando Cabanillas, Karl Dicke
Journal: New England Journal of Medicine (1987)

Adult patients with advanced non-Hodgkin's lymphoma in whom conventional chemotherapy has failed are seldom cured thereafter. We studied 100 such patients with intermediate-grade or high-grade non-Hodgkin's lymphoma who were subsequently treated with high-dose chemotherapy (61 patients) or high-dose chemotherapy plus total-body irradiation (39 patients), with bone marrow transplantation used for hematologic support. Thirty-four patients had disease that had been refractory to primary chemotherapy, and 66 patients had had a complete remission with primary chemotherapy but later relapsed. Before autologous bone marrow transplantation and high-dose chemotherapy, the 66 relapsed patients had also received conventional salvage chemotherapy; 22 had had no response or had had disease progression (a response termed "resistant relapse"), and 44 patients had responded partially or completely (a response termed "sensitive relapse"). After high-dose therapy and bone marrow transplantation, the actuarial three-year disease-free survival was zero in the refractory group, 14 percent in the resistant-relapse group, and 36 percent in the sensitive-relapse group. Patients who had had a complete remission in response to initial chemotherapy had a higher disease-free survival rate than those who had not (P less than 0.001), and patients with sensitive relapse had a higher disease-free survival rate than those with resistant relapse (P less than 0.003). These results should be considered in the planning or interpretation of trials of salvage chemotherapy in adults with non-Hodgkin's lymphoma.
Calcification of Entheses Associated with X-Linked Hypophosphatemic Osteomalacia
Authors: Richard P. Polisson, Salutario Martinez, Maroon Khoury, R. Mack Harrell, Kenneth W. Lyles, Nancy Friedman, John M. Harrelson, Emily Reisner, Marc K. Drezner
Journal: New England Journal of Medicine (1985)

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.
A Problem in Anesthesia Management
Authors: G. Purdell-Lewis
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The article entitled "Permanent Alopecia From Pressure of a Head Strap" (<b>199</b>:747, 1967) was of considerable interest. It is noted, however, that the age of the patient was 4 years and the duration of the anaesthetic 6 1/2 hours. Hence, I feel that in similar cases the answer is not in more careful positioning of the head strap, but rather a change in anaesthetic technique: to use an appropriately sized pediatric orotracheal tube (to reduce dead space) and low-resistance circle or high-flow open anaesthetic circuit. Further, in such a young patient and an operation lasting as long as this, a case can be made for intermittent positive pressure ventilation with use of tubocurarine or halothane to depress respiration. This would ensure maintenance of favorable oxygen and carbon dioxide arterial gas tensions and prevent respiratory acidosis. Further, oxygen consumption would be reduced and the child would be
Abstract 1472: Assessment of CTC-based pharmacodynamic biomarkers in NCI clinical trials of targeted anticancer therapeutics.
Authors: Lihua H. Wang, Shivaani Kummar, Thomas D. Pfister, Priya Balasubramanian, Ralph E. Parchment, Joseph E. Tomaszewski, James H. Doroshow, Robert J. Kinders
Journal: Cancer Research (2013)

Abstract Circulating tumor cells (CTC) potentially represent a substitute for biopsy in assessing drug effects on targets. We have previously reported development and validation of CTC-based pharmacodynamic (PD) biomarker assays that directly examine drug-induced responses (e.g. a DNA damage marker γH2AX, and a tumor suppressor marker p16/INK4a). Here, we summarize our results to date and assess utility of CTC-based biomarkers in patients undergoing clinical trials of targeted anti-cancer therapeutics. Across eight NCI Phase 1 and 2 trials in a variety of solid tumors, the portion of the population statistically evaluable is approximately 30% for all trials; the CTC biomarker statistical evaluation is limited by the total number of CTCs collected from each tube of blood. From data obtained from multiple trials of topoisomerase1 and PARP inhibitors, the γH2AX-positive CTC baseline level was less than 20% in 34 of 50 patients. The fraction of CTCs expressing γH2AX independent of changes in the total CTC count, increased in patients following treatment with different topoisomerase 1 inhibitors alone or in combination with other drugs. Furthermore, correlations between γH2AX levels and overall responses were demonstrated in patients with refractory cancer in a phase II randomized trial of the combination of Veliparib with metronomic oral cyclophosphamide. Pharmacodynamic studies measuring re-expression of the tumor suppressor p16 in response to the epigenetic therapy regimen of 5-fluoro-2-deoxycytidine plus tetrahydrouridine yielded similar results on the number of patients evaluable using CTCs in the NCI intramural patient population. Given the limitations of surface molecule-based CTC methods, we are developing and evaluating an antibody-independent CTC capture technology to analyze biomarkers, starting in small animals using lower blood volumes and in patients with a variety of advanced epithelial and non-epithelial cancers. Our studies indicate that assessment of CTC-based PD biomarkers has value for rapidly assessing proof of mechanism in the clinical development of molecularly targeted anticancer therapeutics. Funded by NCI contract # HHSN261200800001E Citation Format: Lihua H. Wang, Shivaani Kummar, Thomas D. Pfister, Priya Balasubramanian, Ralph E. Parchment, Joseph E. Tomaszewski, James H. Doroshow, Robert J. Kinders. Assessment of CTC-based pharmacodynamic biomarkers in NCI clinical trials of targeted anticancer therapeutics. [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 1472. doi:10.1158/1538-7445.AM2013-1472
PTU-172 Oesophageal cancer risk: results of a prospective cohort with Barrett's oesophagus
Authors: B T Theron, H Padmanabhan, H Aladin, B T Cooper, N Trudgill
Journal: Gut (2012)

<h3>Introduction</h3> Widely varying rates of oesophageal adenocarcinoma (OAC) in patients with Barrett9s oesophagus (BO) have been reported, with recent studies and meta-analyses suggesting a lower incidence, affecting the cost effectiveness of surveillance. However, advances in endoscopic therapy for dysplasia suggest surveillance should potentially be extended to more elderly patients. We have therefore examined long term outcomes in a BO cohort. <h3>Methods</h3> BO patients with intestinal metaplasia from a prospectively maintained database (1982–2008) were analysed. Cancer registrations and causes of death from death certificates were obtained from the NHS information centre for health and social care and cross-referenced with local data. The incidence of OAC was calculated as events per 100 person years (% per year) of follow-up. Regression analysis was used to determine associations between the OAC development and age, sex, hiatus hernia, BO length, strictures and ulcers. Standardised mortality ratios were calculated using age adjusted indirect standardisation. Patients were subdivided into those suitable for surveillance and those deemed unfit due to age or comorbidity. <h3>Results</h3> 713 (429 male, median age at diagnosis 64 years, range 30–92) BO patients were in the cohort. After a median of 11 (range 2–24) years of follow-up, 38 (27 male, median age 70 (48–90)) patients were diagnosed with OAC. The incidence of OAC was 0.5% per annum (p.a.). In patients considered suitable for surveillance, the incidence was 0.6% p.a. compared to 0.3% (p=0.06) in those not surveyed due to age or comorbidity. The rate of OAC in surveyed patients from 1982 to 1989 was 0.6% p.a., from 1990 to 1999 0.4% and from 2000 to 2008 0.5%. OAC was associated with increasing BO length (OR 1.11 (95% CI 1.01 to 1.13), p=0.03), but not with male sex (OR 1.66 (95% CI 0.8 to 3.4)), hiatus hernia (OR 1.31 (95% CI 0.68 to 2.57)), ulcer (OR 0.39, (95% CI 0.01 to 1.65)) or stricture (OR 0.97 (95% CI 0.37 to 3.1)). Standardised mortality ratios was elevated for the whole group at 181 (95% CI 162 to 181). Increasing age was associated with dying from OAC (OR 1.09 (95% CI 1.07 to 1.11) but not with the development of OAC (OR 0.99, (95% CI 0.96 to 1.01). 41% deaths in the cohort were from cardiorespiratory disease. <h3>Conclusion</h3> The risk of OAC within this prospectively surveyed cohort was 0.5% per annum, which is higher than recent estimates. The rate of OAC in surveyed BO appears to have remained stable over the last 3 decades. Increasing length of BO is associated with a higher risk of developing OAC. BO is associated with an excess mortality risk and this is mainly related to cardiorespiratory disease. <h3>Competing interests</h3> None declared.
Acute Coronary Insufficiency — Coronary Occlusion after Intermittent Ischemic Attacks
Authors: William A. Neill, Thomas P. Wharton, Joan Fluri-Lundeen, Ira S. Cohen
Journal: New England Journal of Medicine (1980)

We used angiography in a prospective study of the coronary circulation in patients with acute coronary insufficiency. Reversible ST-T changes during the acute illness corresponded anatomically with severely narrowed coronary arteries (80 to 95 per cent stenosis). Angiograms repeated four months later showed new complete occlusions in nine of 30 severely stenotic arteries. Eight of the new occlusions occurred in severely narrowed arteries previously correlated with regional ST-T changes. Six patients had myocardial infarctions, five of which corresponded with the site of a new occlusion. These results provide indirect evidence that the acute coronary-insufficiency syndrome commonly represents intermittent transient coronary-artery occlusion and a threat of new permanent occlusion of the same artery. Myocardial infarction in these patients appeared to occur as a complication of the new occlusion.
Sequestered Nodular Goiter
Authors: James C. Sisson, Robert W. Schmidt, William H. Beierwaltes
Journal: New England Journal of Medicine (1964)

THE possibility that the mechanical action of neck muscles can, in rare cases, sever a projecting portion of the thyroid gland has been recognized for over fifty years.1 This process is most likely to occur in a nodular colloid goiter. Cases of colloid nodules separate from the thyroid gland were excluded from several series describing the malignant so-called lateral aberrant thyroid tumor,2 3 4 5 6 but no detailed description of the former entity was found.The present report describes 4 patients who were found at operation to have histologically benign thyroid tissue in cervical-lymph-node areas entirely separate from the thyroid gland.Case Reports . . .
Scintiscan Demonstration of Localized Bowel Loop Inflammation
Authors: ASEEM BHATNAGAR, PUSHPA MISHRA, AJAY KUMAR SINGH, VIJAY TANEJA, UDAY P. S. CHAUHAN, KRISHAN SAWROOP
Journal: Clinical Nuclear Medicine (1996)

A 60-year-old man with localized small bowel inflammation underwent abdominal scintigraphy with Tc-99m human polyclonal immunoglobulin G and two experimental inflammation-seeking agents, Tc-99m dextran and Tc-99m citrate. The abnormal loop was visualized in all the three studies. Additionally, the Tc-99m dextran study revealed exudation and luminal transit of the tracer suggestive of regional protein-losing enteropathy. The authors conclude that Tc-99 dextran and Tc-99 citrate are clinically suitable inflammation-seeking agents that need further evaluation, especially for locating abdominal inflammations.
Second malignancies in patients with primary central nervous system lymphoma
Authors: J. Wang, J. S. Pulido, B. P. O'Neill, P. B. Johnston
Journal: Neuro-Oncology (2014)

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma with distinctive biological behaviors. The evolving treatment of PCNSL has greatly improved the outcome for patients with this disease and has stimulated interest in second malignancies (SMs) in patients diagnosed with PCNSL. The records of 129 cases of PCNSL at Mayo Clinic, diagnosed between January 1, 1988, and November 26, 2012, were reviewed. Data on clinical characteristics, laboratory parameters, treatments, outcomes, and SMs were collected. The mean follow-up time was 44.8 months (range, 0.5–240 months; median, 28.0 months). Altogether, 28 cases with 30 (23.26%) SMs were identified. Twenty (15.50%) patients had prior or synchronous SM. Ten (7.76%) patients developed a subsequent primary cancer after PCNSL. The most common sites of prior or synchronous SMs were prostate (4/20), skin (4/20), and gastrointestinal (3/20). The most common site of the subsequent SM was skin (4/10). Two cases were identified with both prior SM and subsequent SM. Second malignancies in cases with PCNSL were not uncommon and occurred in nearly a quarter of our cohort. Nonmelanoma skin cancers were frequently seen. Therefore, screening for SMs should also be considered in long-term follow-up of patients with PCNSL. In addition, the high incidence of subsequent cancer, synchronous cancer, and frequently seen nonmelanoma skin cancers may all indicate an immunosuppressed state in patients with PCNSL.
Abstract 229: Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase non-receptor type 14
Authors: Peng Zhang, Zhenghe Wang
Journal: Cancer Research (2012)

Abstract Protein tyrosine phosphatases (PTPs) are thought to be potentially important regulators in tumorigenesis as antagonists of protein tyrosine kinases (PTKs). Among them, Protein tyrosine non-receptor type 14 (PTPN14) has been shown to be mutated in both colorectal and breast cancers. However, little is known about the cellular signaling pathways it regulates. In order to determine whether PTPN14 has causative roles in tumorigenesis, we set out to identify substrates of PTPN14 and shed light on the mechanism why it is mutated in different tumor types. In this study, we report the identification of p130Cas, a scaffolding molecule, as a substrate of PTPN14 through a proteomic approach. We show that PTPN14 specifically dephosphorylates p130Cas at tyrosine 128 by shRNA knockdown and overexpression. We also demonstrate p130Cas is a direct substrate of PTPN14 by substrate trapping and in vitro phosphatase assays. We then mutate tyrosine 128 residue to phenylalanine in DLD1 and RKO, two different colorectal cell lines, to study the biological functions of this phosphosite. The mutant cells show reduced tumorigenicity based on colony formation and soft agar assays. However, the phenotypes diverge between the mutant cells from the two cell lines when we test the effect of the mutation on tumor growth in xenograft model. RKO Y128F mutant cells display significantly reduced tumor volumes while DLD1 Y128F mutant cells do not. In addition, RKO Y128F mutant cells are less invasive than parental cells in Matrigel but DLD1 Y128F mutant cells are surprisingly more invasive. We find that AKT is not fully activated in both mutant cells, which is likely the cause of the common phenotypes. However, phospho-ERK is up-regulated in DLD1 mutant cells possibly due to a compensatory mechanism but not in RKO mutant cells since ERK is already constitutively active in RKO cells, which explains the discrepancies in phenotypes mentioned above. Last, Src is shown to be the kinase of p130Cas Y128. When the phosphorylation of p130Cas Y128 is surveyed in six commonly used colorectal cancer cell lines, the phosphorylation levels are found to be correlated with the sensitivities to Src inhibitor. Thus, p130Cas Y128 phosphorylation can be utilized as a prognostic marker for Src inhibitors that are already in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 229. doi:1538-7445.AM2012-229
DOOR-TO-DIURETIC TIME: A PROMISING STRATEGY FOR IMPROVING DELIVERY OF CARE TO PATIENTS HOSPITALIZED WITH DECOMPENSATED HEART FAILURE, A COMMUNITY-BASED SINGLE CENTER EXPERIENCE
Authors: Vasvi Singh, Saurav Luthra, Varda Singhal, Neelima Divakaran, Arnel Magno, Mahesh Krishnamurthy, Ruth Kouides
Journal: Journal of the American College of Cardiology (2015)