tbuckley/cabot-search huggingface dataset:
Abstract 1940: Reg4 induces the expression of D-type cyclins and associated kinases to induce mitotic division of human colorectal cancer cells
Authors: Kumar S. Bishnupuri, Satheesh K. Sainathan, Qizhi Luo, Brian K. Dieckgraefe
Journal: Cancer Research (2011)

Abstract Background: Cyclins and cyclin-dependent kinases (CDK) are important component of the cell cycle machinery. D-type cyclins are positive regulators of cell cycle and a known target of Wnt/β-Catenin signaling. Cyclin D1 and cyclin D3 play a prominent role in differentiation and proliferation and is highly upregulated in many cancers. Recent studies also showed frequent upregulation of regenerating (Reg) gene 4 expression in many human gastrointestinal (GI) malignancies including colorectal cancer (CRC). We further observed a Reg4-mediated increase in β-Catenin expression and its subsequent nuclear translocation. Therefore, we tested the hypothesis that Reg4 induces the expression of D-type cyclins and associated kinases to induce the mitotic division of human CRC cells. Methods: Real time RT-PCR and western blot analyses were performed to determine the effects of Reg4 treatments on the expression of D-type cyclins and associated kinases. Mitotic and MTT assays were performed to determine its association with regulation of mitotic division and proliferation of human CRC cells. Results: Following real-time RT-PCR and western blot analyses we observed a time-dependent increase in cyclin D1 and D3 expression following the addition of recombinant human Reg4 (rhR4) to the cultures of HCT116 and HT29 human CRC cells. Furthermore, addition of rhR4 to the cell cultures also led to an increased expression of CDK4 and CDK6, the known kinase partners of cyclin D. We previously observed the involvement of Akt kinase, GSK-3β, and β-Catenin activities in mediating Reg4-signaling. Therefore, in the present study we utilized a specific Akt inhibitor as an antagonist and SB216763, an inhibitor of GSK-3β as an agonist of Reg4-signaling and examined their effects on expression of D-type cyclins and mitotic index of human CRC cells. Treatments of specific Akt inhibitor (10 μM) to the human CRC cells significantly inhibited the expression of cyclin D1 and D3, and subsequently inhibited their mitotic index. Furthermore, an addition of rhR4 (200 nM) to the cultures of human CRC cells pretreated with specific Akt inhibitor (10 μM) did not increase the expression of these cyclins, hence the mitotic index of human CRC cells. In addition, the treatments of SB216763 (10 μM) positively modulated the Reg4-signaling and led to significant increases in the expression of D-type cyclins, hence mitotic index of human CRC cells. Conclusions: These results suggest that Reg4 is a potent regulator of mitotic division of human CRC cells and involves Akt kinase and GSK-3β as important mediators to induce the expression of D-type cyclins. 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 1940. doi:10.1158/1538-7445.AM2011-1940
Abstract 3370: DNA repair in glioma stem cell-mediated radiation resistance
Authors: Maricruz Rivera, Anita Hjelmeland, Jeremy Rich
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme is the most common type of primary brain cancer in adults and has a 14-month median survival after diagnosis. This low survival is due to resistance to the currently available therapies, which include surgery, radiation, chemotherapy, and anti-angiogenic drugs. Resistance to chemotherapy and radiation in these tumors has been linked to a subgroup of highly tumorigenic cells, called glioblastoma stem cells (GSCs), that resemble normal neural progenitor cells. GSCs have the ability to self-renew, differentiate into various lineages, and re-propagate the tumor, making GSCs an attractive target for treatment. Radiation-treated GSCs retain their tumorigenic capacity and have decreased apoptosis compared to non-GSCs. In addition, GSCs have enhanced DNA damage response activation and faster DNA double-stranded break (DSB) resolution relative to non-GSCs after exposure to ionizing radiation (IR). Exposure to low dose radiation induces DSBs, which are repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). Targeting key proteins involved in HR, such as RAD51, has been shown to reduce glioma cell viability. We are investigating the molecular mechanisms by which DNA repair mediates radiation resistance in GSCs, with some lead candidates identified. Based on a DNA repair gene array, several candidates were identified to be preferentially expressed in GSCs. Current work is focusing on targeting these genes and elucidating their role in radiation resistance. 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 3370. doi:1538-7445.AM2012-3370
Haemodynamic unloading reverses occlusive vascular lesions in severe pulmonary hypertension
Authors: Kohtaro Abe, Masako Shinoda, Mariko Tanaka, Yukimitsu Kuwabara, Keimei Yoshida, Yoshitaka Hirooka, Ivan F. McMurtry, Masahiko Oka, Kenji Sunagawa
Journal: Cardiovascular Research (2016)

An important pathogenic mechanism in the development of idiopathic pulmonary arterial hypertension is hypothesized to be a cancer-like cellular proliferation independent of haemodynamics. However, because the vascular lesions are inseparably coupled with haemodynamic stress, the fate of the lesions is unknown when haemodynamic stress is eliminated. We applied left pulmonary artery banding to a rat model with advanced pulmonary hypertension to investigate the effects of decreased haemodynamic stress on occlusive vascular lesions. Rats were given an injection of the VEGF blocker Sugen5416 and exposed to 3 weeks of hypoxia plus an additional 7 weeks of normoxia (total 10 weeks) (SU/Hx/Nx rats). The banding surgery to reduce haemodynamic stress to the left lung was done at 1 week prior to (preventive) or 5 weeks after (reversal) the SU5416 injection. All SU/Hx/Nx-exposed rats developed severe pulmonary hypertension and right ventricular hypertrophy. Histological analyses showed that the non-banded right lungs developed occlusive lesions including plexiform lesions with marked perivascular cell accumulation. In contrast, banding the left pulmonary artery not only prevented the development of but also reversed the established occlusive lesions as well as perivascular inflammation in the left lungs. Our results indicate that haemodynamic stress is prerequisite to the development and progression of occlusive neointimal lesions in this rat model of severe pulmonary hypertension. We conclude that perivascular inflammation and occlusive neointimal arteriopathy are driven by haemodynamic stress.
P204 Travel with CPAP machines: how frequent and what are the problems?
Authors: S. Faruqi, P. Carveth-Johnson, A. O. C. Johnson
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Obstructive sleep apnoea (OSA) is common and most patients are relatively young. CPAP is the standard treatment. This questionnaire survey aimed to improve the understanding of the problems which patients on CPAP face during travel and while away from home. <h3>Methods</h3> 150 patients on CPAP were randomly selected from our patient database and sent a postal questionnaire. They were asked the number of times they had travelled in the last 2 years and specific questions about the last three trips. These included mode of travel, duration of trip, change in CPAP use, problems with transport and use of CPAP. Patients were asked to specifically document whether they used CPAP during travel. All patients are offered a letter regarding their CPAP therapy to facilitate travel. <h3>Results</h3> 101 questionnaires were returned (men=69, mean age=60.5 years). 58 (men=50, mean age 59.4 years) had travelled in the last 2 years on 211 occasions. Data were collected for 139 trips. In 13 trips the CPAP machine was not taken. Reasons included weight, space and check in concerns. 84 trips were within Europe and 7 to North America. 93 trips were by air. On 22 trips, respondents reported the “CPAP letter” was needed for check in. In 7 of the 93 trips by air, problems with checking in the CPAP machine were encountered. In all but 4 trips the CPAP machine was carried as hand luggage. In 33 trips problems with use of CPAP due to the short power cord was reported. CPAP was used less often abroad. CPAP was rarely used during travel. Individual statements highlighted problems with security and check-in. <h3>Conclusions</h3> Patients with OSA travel abroad frequently and usually take their CPAP machine with them. In a significant number there are problems with check-in of the CPAP machine and we strongly recommend patients are provided with a “CPAP letter”. Improved dissemination of information is needed to patients and airport staff regarding OSA and CPAP. We recommend patients carry extension cords and power adaptors. The reason for less use of CPAP abroad is not clear and needs further explanation.
A Case of Primary Leptomeningeal Melanoma Evaluated on FDG PET/CT
Authors: Michael J. Golden, William H. Wheir, Joanna Katzman, Zulfiqar A. Turk, Michael F. Hartshorne
Journal: Clinical Nuclear Medicine (2011)

Primary leptomeningeal melanoma is a rare and aggressive tumor caused by melanin containing cells in the pia mater, which may malignantly degenerate. Despite the advances in neuroimaging, it remains a difficult diagnosis. We report a case of 51-year-old man who presented with headache, nausea and vomiting, fatigue, and left hip pain. MRI showed diffuse disease of the leptomeninges, most notably in the cauda equina. Subsequent PET/CT was performed, in part to identify a site of suitable biopsy. No disease was identified outside the central nervous system, and open biopsy of the cauda equina demonstrated primary leptomeningeal melanoma.
METABOLISM OF 15-p-123I-PHENYLPENTADECANOIC ACID (IPPA) IN A CANINE MODEL OF REGIONAL ISCHEMIA.
Authors: Marck P. Hudon, Donald M. Lyster, W. R. Eric Jamieson, A. Karim Qayumi, Craig Sartori, Hayes Dougan
Journal: Clinical Nuclear Medicine (1988)

Hudon, Marck P.; Lyster, Donald M.; Jamieson, W. R. Eric; Qayumi, A. Karim; Sartori, Craig; Dougan, Hayes Author Information
Abstract 4049: AP2A1 is required for UV-induced EGFR nuclear translocation
Authors: Sheng-Chieh Hsu
Journal: Cancer Research (2011)

Abstract Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved in cell proliferation, differentiation and survival. Aberrant expression and activation of EGFR have shown to cause various types of human and frequently associated with poor prognosis, metastasis and chemoresistance. Interestingly, this cell membrane receptor, which has been extensively studied, not only transduces signals from the cell membrane, but can also translocate into the nucleus and play a role in gene regulation, DNA repair and chemoresistance. Nuclear translocation of EGFR could be induced by ligand-dependent and ligand-independent manners including ionizing radiation (IR), cisplatin and UV treatment. However, the molecular mechanisms of EGFR nuclear translocation induced by DNA damage agents remain unclear. Here, we identify EGFR interacts with AP2A1 upon UV treatment using proteomic approach. The AP2A1 is the alpha 1 adaptin subunit of the adaptor protein 2 (AP2) complex found in clathrin coated vesicles. Knock-down AP2A1 expression inhibits the UV-induced EGFR nuclear translocation. Thus, we demonstrate here AP2A1 is required for UV-induced EGFR nuclear translocation. 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 4049. doi:10.1158/1538-7445.AM2011-4049
Controversies in management: Should methionine be added to every paracetamol tablet? (No: The risks are not well enough known)
Authors: A L Jones, P C Hayes, A T Proudfoot, J A Vale, L F Prescott
Journal: BMJ (1997)

Each year in the United Kingdom roughly 2600 million tablets of paracetamol are sold over the counter and 600 million supplied on prescription (Paracetamol Information Centre Study, November 1993). Paracetamol overdose is common in many parts of the world.

In studies in Britain and America paracetamol was the commonest drug used in overdose, being taken in about 48% of overdoses in Oxford1 and 5% in America.2 Clinicians in general, and those working in liver transplant units in particular, are increasingly aware of the problems raised by the liver damage caused by paracetamol, and pressure is growing to find some preventive measure. Adding the antidote methionine3 to paracetamol tablets is attractive, but because most people who take overdoses act impulsively it would have to be added to every formulation to be of maximum value. The critical issue then is whether the vast numbers of responsible users of paracetamol should have no choice but to take it with methionine in order to protect the minority who take overdoses.

Overdose of paracetamol causes hepatotoxicity ranging from mild, asymptomatic derangement of liver function to fulminant hepatic failure and death. Official statistics considerably overestimate the number of deaths from paracetamol poisoning.4 Thus in 1990, of 547 deaths attributed to paracetamol in England and Wales, only 150 were substantiated after review.5 The official returns include people who never reach hospital …
Abstract 4554: A docking domain directed inhibitor targeting ERK regulated F-site substrates.
Authors: Jun Zhang, Taiji Oashi, Ramin Samadani, Kerrick Nevels, Kimberly Burkhard, Deva Priyakumar, Prabhu Raman, Steven Fletcher, Edvin Pozharsky, Paul Shapiro, Alexander MacKerell
Journal: Cancer Research (2013)

Abstract Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are ubiquitously expressed in almost all tissues and cell types. Accordingly, ERK1/2 regulate a diversity of cellular processes by phosphorylating more than 150 substrate proteins. With its constitutive activation being frequently implicated in human malignancies, ERK has been an appealing target in anti-cancer drug development. However, currently available ERK1/2 inhibitors are ATP-competitive. Since these ERK inhibitors block all ERK functions, the potential for side effects in normal tissues and cells may limit their potential of being developed into therapeutic agents. To overcome this limitation, we used a combination of computational and experimental methods to develop small molecular weight inhibitors that target ERK-substrate docking domains. Here we report the identification, characterization and optimization of a compound with a thienyl benzenesulfonate scaffold that specifically inhibits substrates containing an F-site or DEF (docking site for ERK, FXF) motif. Our X-ray crystallography data showed that this compound bound to a pocket in the vicinity of the F-site docking domain on ERK. Biological analysis further demonstrated that this compound and its analogs could preferentially inhibit phosphorylation and function of F-site-containing ERK substrates, and that these compounds preferentially inhibited growth of melanoma cells harboring a V600E B-Raf mutant. Additionally, this compound was shown to inhibit the phosphorylation of specific PKC isoforms via an ERK dependent mechanism. These findings represent the first identification and validation of chemicals that selectively inhibit ERK substrates and signaling events through ATP-independent mechanisms. These compounds have potential utility for elucidating the complex biological roles of ERK1/2 and development into novel anti-cancer agents. Citation Format: Jun Zhang, Taiji Oashi, Ramin Samadani, Kerrick Nevels, Kimberly Burkhard, Deva Priyakumar, Prabhu Raman, Steven Fletcher, Edvin Pozharsky, Paul Shapiro, Alexander MacKerell. A docking domain directed inhibitor targeting ERK regulated F-site substrates. [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 4554. doi:10.1158/1538-7445.AM2013-4554
ANTEROSEPTAL ST ELEVATION MYOCARDIAL INFARCTION AND NON-DOMINANT RIGHT CORONARY ARTERY LESION INVOLVING ACUTE MARGINAL BRANCH: A DILEMMA IN DECISION MAKING
Authors: Jeffrey J. Heslop, Karthiek Narala, Sandeep Banga, Sudhir Mungee
Journal: Journal of the American College of Cardiology (2015)
Abstract 4907: Knockdown of MMP-9 inhibits radiation-induced invasive phenotype, angiogenesis and tumor growth in glioma cancer stem cells.
Authors: Chandramu Chetty, Shivani Ponnala, Meena Gujrati, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Gliomas contain a small number of treatment-resistant glioma stem cells (GSCs). It is thought that tumor regrowth or recurrence originates from GSCs, thus rendering GSCs an attractive target for novel treatment approaches. GSCs are also resistant to conventional chemotherapy and radiation therapy, and a low dose of ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. In the present study, an isolated glioma stem cell population exhibited a significant differential expression of MMP-9 and a low dose of irradiation enhanced MMP-9 expression levels. Transfection of GSCs with pMMP-9-Si inhibited radiation-induced MMP-9 activity and protein levels as well as cell proliferation. The sphere de-differentiating and invasive ability of GSCs were also reduced in MMP-9 knockdown cells when compared with mock and pSV controls. MMP-9 knockdown led to the induction of apoptotic cell death as determined by FACS and TUNEL analyses, and caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. pMMP-9-Si transfection also inhibited radiation-induced angiogenesis in vitro and in vivo in GSCs. Further, pMMP-9-Si treatment inhibited pre-established glioma tumor growth in an intracranial model. In addition, GSC xenograft tissue sections from mice that were treated with MMP-9 siRNA showed reduced expression of VEGF and the angiogenic marker, CD31. Indeed, TUNEL analysis of tumor sections collected from the combination group of pMMP-9-Si and irradiation revealed more apoptotic cells. These results validate the usefulness of targeting MMP-9 and provide a novel perspective in the treatment of the cancer stem cell population with its higher resistance to radiotherapy. Citation Format: Chandramu Chetty, Shivani Ponnala, Meena Gujrati, Jasti S. Rao. Knockdown of MMP-9 inhibits radiation-induced invasive phenotype, angiogenesis and tumor growth in glioma cancer stem cells. [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 4907. doi:10.1158/1538-7445.AM2013-4907
Lymphoscintigraphic Demonstration of Chyle Leak After Kidney Transplantation and Gamma Camera Detection of Radioactivity in Chylous Aspirate
Authors: Jin Kyoung Oh, Hye Eun Yoon, Yong-An Chung
Journal: Clinical Nuclear Medicine (2014)

Iatrogenic chyle leak with chyloma formation is a rare complication of kidney transplantation resulting from injury to the lymphatics. We present a case of a 53-year-old man who complained of right leg swelling 2 months after kidney transplantation for chronic renal failure. Abdomen CT showed loculated fluid collection around the transplanted kidney. Lymphoscintigraphy demonstrated chyle leak in the right iliac fossa, and subsequent ultrasound-guided aspiration of the chyloma showed radioactivity as detected by gamma camera. After drainage insertion, the amount of collected fluid gradually decreased, and right leg edema was relieved.
Case 62-1962
Authors: Rita M. Kelley, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A fifty-two-year-old man was admitted to the hospital because of a mass in the parotid gland.During the previous year the patient was aware of a gradually enlarging, painless mass in the left parotid region, accompanied by lethargy, fatigue and a loss of 15 pounds in weight. The hemoglobin fell from 92 to 65 per cent of normal during the five months before entry.Physical examination revealed a well nourished man with striking cervical lymphadenopathy bilaterally and a 5-cm., movable, nontender mass in the left parotid area. Lymph nodes were also palpable in the . . .
P46 Patient Activity Levels and Oxygen Device Preference: An RCT Comparing Refillable Cylinders (HomefillTM) with Usual Ambulatory Device
Authors: J Turnbull, L McDonnell, L Osman, J Bott, T Prevost, AC Davidson
Journal: Thorax (2012)

<h3>Introduction</h3> The benefit of ambulatory oxygen (AO) in patients with hypoxaemia on exercise remains contentious. Often AO is not used in the way the prescribers envisage. Device suitability or poor understanding about the benefits of AO may mean patients remain hypoxic on activity and/or avoid exercise. <h3>Objective</h3> To assess patients activity and preference using Homefill<sup>TM</sup> versus usual AO device in a mixed population of patients with exercise hypoxaemia and/or LTOT. Homefill<sup>TM</sup> allows patient refill of oxygen cylinders (1.9 L) as needed using a compressor. <h3>Methods</h3> Inclusion criteria included current use of AO and stable physical condition. AO prescription was optimised for each device. Patients were randomised to usual AO then HomefillTM for 6 wks or vice versa. Tri-axial activity monitors were used during the last week. Patient preference was identified by questionnaire. Weekly calls encouraging activity and AO use were made. If patients suffered an inter-current illness, the trial arm was extended by 2 wks; those with &gt;1 illness were withdrawn. Power calculation indicated a sample of 40 subjects was required to detect a difference of 1,000 domestic activity counts at a 5% significance level with 80% power. <h3>Results</h3> 70 patients met the inclusion criteria and 40 enrolled. Mean age 66 yrs, 17 males, 70% had COPD with median FEV1 41% predicted (range 27–71%), restrictive median FVC 70% predicted. 29 complete data sets were collected. There were 9 episodes of AECOPD. Fifteen patients required the highest 02 pulsed setting on HomefillTM There was no statistically significant difference in mean daily activity counts when using HomefillTM compared to usual AO. A decline in activity counts was observed in both cohorts during the second period. Eighteen patients elected to keep HomefillTM of whom 11 previously used LOX as their usual AO. <h3>Conclusions</h3> Homefill was equivalent to usual provision of AO and was preferred by the majority. Disappointingly, regular phone encouragement failed to increase activity levels. Activity levels were very low and highly variable reflecting advanced disease/deconditioning. <h3>Implications for Practise</h3> Patient use and preference of AO device includes non physiological aspects. AO maybe best targeted at patients before exercise tolerance is severely limited.