tbuckley/cabot-search huggingface dataset:
Abstract 5122: Regulation of integrin trafficking by Rab proteins
Authors: Nazarul Hasan, Chuan Hu
Journal: Cancer Research (2010)

Abstract Integrins, the major receptors for cell adhesion to the extracellular matrix, are synthesized in the endoplasmic reticulum, transported in vesicles, and delivered to the plasma membrane or the cell surface by exocytosis. Like other receptors, integrins at the plasma membrane are constantly endocytosed, transported into endosomal compartments and then recycled back to the surface. Therefore, the density of integrins at the cell surface is ultimately determined by the balance between two vesicle trafficking events: endocytosis and exocytosis. Rab proteins are small (20-29 kDa) monomeric Ras-like GTPases that regulate vesicle budding, transport and tethering to the target membranes. Rab4, Rab11 and Rab25 function in the endocytic and recycling pathway. In this study, we examined roles of the Rab proteins in integrin trafficking. Silencing of Rab11 in HeLa cells had neither obvious effects on cell surface or total cellular expression of α3, α5 and β1 integrins nor on cell migration. Silencing of Rab25 reduced the surface expression of all three integrins and inhibited chemotactic migration. Surprisingly, Rab4 silencing dramatically increased both cell surface and total cellular expression of the integrins, and inhibited cell migration as well. These data suggest that Rab25 is required in integrin trafficking to the cell surface, and that Rab4 negatively regulates the expression and trafficking of integrins. These data support the notion that reduced or excessive integrins at the cell surface diminish cell motility. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5122.
Useful endoscopic findings for early diagnosis of ulcerative colitis associated colorectal cancer
Authors: Y Sato, S Takagi, H Aizawa, H Yokoyama, S Takahashi, Y Kakuta, M Tosa, A Mochida, E Nomura, S Takahashi, Y Kinouchi, T Shimosegawa
Journal: Endoscopy (2008)

Ulcerative colitis is a chronic inflammatory bowel disorder associated with a high risk of colorectal cancer [1]. Endoscopic diagnosis of early ulcerative colitis-associated colorectal cancer or precancerous lesions is very difficult [2] [3] [4].
AB0639 Serologic status and illness appraisal modulate key patient reported outcomes in primary sjogrens syndrome
Authors: B.M. Segal, G. McElvain, L. Henn, R. Prosser, K. Rudser, N. Rhodus, K.L. Moser
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> PSS is characterized by pain, fatigue, lack of a cure, uncertainty and chronicity. Psychological factors are known to modulate health status in persons with chronic illness, but little data is available in PSS. Illness perceptions (especially perceived consequence and perceived control) are important factors influencing medical, psychological and behavioral outcomes in patients with rheumatic disorders. <h3>Objectives</h3> The aim of this study was to use a validated instrument: the Illness Perceptions Questionnaire (IPQ-R) to investigate potential links between illness perceptions and functional outcomes in patients with primary Sjogren’s syndrome (PSS) and to compare illness representations in patients with different disease characteristics. We compared seropositive and seronegative PSS patients to assess the effects of serologic status and illness perceptions on key outcomes including fatigue, pain and health status. <h3>Methods</h3> Demographics, clinical characteristics (sicca symptoms and objective sicca measures), health outcomes: fatigue (FSS), pain(BPI), sleep quality(PSQI), mood (HADS), generic health status (SF-12) and illness perceptions (IPQ-R) were evaluated by survey. Relationships between illness perceptions, clinical characteristics and SF-12 domains were assessed by spearman rank correlation. Psychological and clinical characteristics were compared in the two groups by t test and Pearson’s Chi-Squared Test. <h3>Results</h3> PSS patients (N=123) by AECG criteria were compared based on serologic status (SSA/and or SSB positive vs. SSA/SSB negative) Seronegative (N=45) and seropositive subjects (N=78) were similar in gender (95% F), education (77% college), ethnicity (95% Caucasian), whereas seronegative patients were slightly older (63 yrs. vs. 58 yrs., p=.004). The seronegative group reported greater pain severity (p=.003) and had more negative physical domain SF-12 scores (p=.021) despite a trend toward less severe sicca and similar illness perceptions in all domains of the IPQ-R. Pessimistic beliefs about the consequences of illness were associated with fatigue, with pain severity and with reduced physical function in both patient groups. Mental domain SF-12 scores were negatively associated with fatigue and depression in the seropositive and with fatigue and anxiety in the seronegative group. <h3>Conclusions</h3> In other chronic illnesses in which fatigue and pain are prominent, coping styles, self-efficacy and catastrophizing are predictive of health outcome. We found that psychological factors, particularly pessimistic beliefs about the consequences of illness, contribute to fatigue and pain as well as to health status in PSS. Assessment of illness perceptions and appropriately designed cognitive behavioral interventions could be helpful to reduce fatigue, pain and psychological distress. <h3>Disclosure of Interest</h3> None Declared
STRONTIUM-89: TREATMENT RESULTS IN PATIENTS WITH PAINFUL METASTATIC PROSTATE &amp; BREAST CANCER IN BONE.
Authors: Ralph G. Robinson, David F. Preston, Glen M. Blake, Val Lewington, Jay A. Spicer, Duncan M. Ackery
Journal: Clinical Nuclear Medicine (1988)

Robinson, Ralph G.; Preston, David F.; Blake, Glen M.; Lewington, Val; Spicer, Jay A.; Ackery, Duncan M. Author Information
Lung Herniation after Cough-Induced Rupture of Intercostal Muscle
Authors: Matthew O'Shea, Morgan Cleasby
Journal: New England Journal of Medicine (2012)

A 40-year-old woman with asthma presented with pleuritic chest pain of acute onset. She had been coughing markedly for 2 weeks and had been treated with antibiotics for a lower respiratory tract infection. There was no history of trauma.
Drug-Induced Effects on Erlotinib Metabolism
Authors: Olivier Mir, Benoit Blanchet, François Goldwasser
Journal: New England Journal of Medicine (2011)

A woman with lung cancer in whom the usual toxicities from erlotinib did not develop at the standard dose had a tumor response and side effects when the erlotinib dose was increased. Furthermore, the erlotinib dose had to be reduced when fenofibrate was stopped.
An open label phase II trial of BI 2536, a novel Plk1 inhibitor, in patients with metastatic hormone refractory prostate cancer (HRPC)
Authors: H. S. Pandha, A. Protheroe, J. Wylie, C. Parker, J. Chambers, S. Bell, G. Munzert
Journal: Journal of Clinical Oncology (2008)

14547 Background: BI 2536 is a novel, highly selective, potent inhibitor of Polo-like kinase 1 (Plk1), a key regulator of mitotic progression. BI 2536 has demonstrated favorable tolerability and antitumor activity in Phase I trials. We investigated the activity, safety and pharmacokinetics of BI 2536 in patients (pts) with metastatic HRPC. Methods: This open label, single arm Phase II study used a modified Gehan two-stage design. The primary objective was to determine the PSA response rate at 12 weeks according to Prostate Specific Antigen Working Group (PSAWG) criteria. HRPC pts with castrate testosterone levels, PSA progression and a PSA of >10 ng/ml were entered. 15 pts had to complete ≥4 courses to be evaluable for Stage 1 analysis. In case of at least two PSA responders, 35 additional pts were planned for Stage 2. Pts were treated with 200 mg BI 2536 given as a 1h i.v. infusion on Day 1 every 3 weeks. The dose was escalated to 250 mg from cycle 2 onwards in pts with <Grade 2 drug related non-hematologic and <Grade 3 hematologic toxicity. Results: 20 men with a median age of 70 years (range: 56–76) and a median Gleason score of 9 were treated. The median PSA at study entry was 47 ng/ml. Of the 15 evaluable pts entered into Stage 1, 3 were docetaxel pretreated and 11 were chemonaive. There were no PSAWG criteria PSA responders; 9 pts progressed, 6 pts had stable disease with 1 pt achieving a 25% PSA reduction. RECIST evaluation showed stable disease in 5 pts after 4 courses. Overall, BI 2536 was very well tolerated. Neutropenia was the main toxicity observed. At 200 mg dosing, Grade 3/4 neutropenia was observed in 20%, and after escalation to 250 mg, in 73% of pts. There were 2 cases of neutropenic infection requiring hospitalization in the Stage 1 population. Due to the lack of PSA responders the accrual did not continue beyond Stage 1 analysis. Conclusions: BI 2536 was very well tolerated in metastatic HRPC pts, with some indications of antitumor activity by PSA reduction and radiologically stable disease. As the Stage 1 study objectives were not reached, BI 2536 will not be assessed further as a single agent. Ongoing preclinical work is assessing the potential for synergy of BI 2536 in combination therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim
Abstract 1751: Engineered toxin bodies with specific cell kill activity against mesenchymal cells
Authors: Jack P. Higgins, Lee Robinson, John Higley, Kari Grant, Bill Null, Keng Zhu, Jason Kim, Casey Cunningham, Eric Poma
Journal: Cancer Research (2011)

Abstract The epithelial-to-mesenchymal transition is associated with progression and poor outcome in numerous cancers. Discovery of selective agents that target mesenchymal cancer cells has been an area of significant interest. Here we describe the identification of several novel compounds that specifically recognize and kill H358 Non-small cell lung carcinoma (NSCLC) cells that have been transitioned to a mesenchymal phenotype while showing no activity against H358 epithelial cells. These compounds were identified from a screen of a novel biologic library derived from a de-immunogenized Shiga-like toxin 1 A subunit (SLT1A); SLT1A has no intrinsic binding ability of its own but can drive internalization, retrograde transport to the cytosol, and enzymatic inhibition of ribosome activity. This modified library of engineered toxin bodies (ETBs) was created through the insertion of random amino acids near the C-terminus of the SLT1A scaffold to confer selective binding ability of SLT1A while preserving the therapeutic PK and ADME profile of the scaffold. This library of approximately 10⁁15 variants was pre-cleared against epithelial H358 cells and then screened against mesenchymal H358 cells. The screen was performed in an etiology driven manner where the receptor was not known a priori and selection was based on variants ability to induce cell-kill. Sequence convergence was observed as a result of the biopanning and further characterization of a selected group of mesenchymal-specific ETBs is on-going. 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 1751. doi:10.1158/1538-7445.AM2011-1751
Brief Report:<i>Pneumocystis carinii</i>Osteomyelitis in a Patient with Common Variable Immunodeficiency
Authors: Lisa M. Esolen, Mary Beth Fasano, John Flynn, Andrew Burton, Howard M. Lederman
Journal: New England Journal of Medicine (1992)

PNEUMOCYSTIS CARINII is a well-known pulmonary pathogen that has been increasingly identified in extrapulmonary sites in patients with the acquired immunodeficiency syndrome (AIDS).1 2 3 4 5 6 7 We describe a case of pneumocystis osteomyelitis that occurred in a patient with common variable immunodeficiency. It was striking that the patient appeared to have normal cell-mediated immunity, including a blastogenic response to pneumocystis antigen. Case Report A 27-year-old black woman with common variable immunodeficiency presented with a one-month history of increasing pain in the left buttock. Common variable immunodeficiency had been diagnosed five years earlier after an evaluation for recurrent infections of the upper and lower . . .
Abstract 1719: Leptin, an obesity-related adipocytokine, promotes accelerated growth of Wnt-1 mammary tumors and modulates basal-like and luminal tumor markers
Authors: Qiao Zheng, Sarah Smith, Jinling Zhu, Stephen D Hursting, Ofer Reizes
Journal: Cancer Research (2010)

Abstract Over 2/3 of the US population is obese or overweight, a condition associated with increased risk and decreased survival of various cancers including breast cancer. There is a large unmet medical need to identify mechanisms underlying the link between obesity and cancer. The purpose of these studies is to elucidate the obesity-dependent mechanisms promoting aggressive mammary tumor growth. Circulating levels of leptin, an adipocyte-secreted cytokine that regulates body weight, are elevated in obese and overweight individuals. We orthotopically transplanted tumor cells derived from primary spontaneous MMTV-Wnt-1 tumors into morbidly obese leptin-deficient (ob/ob; lack wild-type leptin) and leptin receptor-deficient (db/db; hyperleptinemic) mice. The MMTV-Wnt-1 tumors, like many human breast tumors, are mixed lineage giving rise to tumors expressing both basal and luminal tumor markers. We determined that orthotopic transplant of MMTV-Wnt-1 tumor cells into obese db/db mice, with high serum leptin, leads to accelerated tumor growth. In contrast, transplant into obese ob/ob mice leads to small, disorganized tumors. More importantly, tumors from leptin-deficient ob/ob mice are predominantly comprised of differentiated epithelial (E-cadherin) and myoepithelial (α—SMA and keratin 14) tumors cells and surprisingly lack basal (keratin 5 and 6) and luminal (keratin 8) lineage tumor cells. Indeed, we determined that AKT cell survival/proliferation pathway was suppressed in the tumors from leptin-deficient mice. The phospho-AKT (p-AKT) immunopositive cells were primarily also expressing keratin 6, and not αSMA or keratin 8, indicating that AKT is activated in the keratin 6 basal-like tumor cells. These studies are highly significant because they indicate leptin, elevated in obese patients, promotes aggressive tumor growth by targeting survival, proliferation, and/or differentiation of subpopulations of mammary tumor cells. 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 1719.
Abstract 1724: BRAF inhibition is enhanced by BH3-mimetic through BIM induction.
Authors: Dennie T. Frederick, Roberto A. Salas Fragomeni, Taylor Hoff, Zachary A. Cooper, James W. Mier, Jennifer A. Wargo, Ryan J. Sullivan
Journal: Cancer Research (2013)

Abstract Vemurafenib (Vem) is a highly selective inhibitor of mutant BRAF, FDA-approved for the treatment of patients with BRAF-positive advanced melanoma. While response rates to Vem are high, the emergence of resistance is common, placing high priority in the development of strategies to enhance Vem efficiency. Navitoclax is a BH3-mimetic that binds and inactivates the anti-apoptotic proteins BCL-2, BCL-xl, and BCL-w and leads to apoptosis in tumors with low expression of another anti-apoptotic protein, MCL-1. Our data demonstrates that treatment of BRAF-mutant melanoma patients with Vem is associated with decreased expression of MCL-1 in addition to an increase in the pro-apoptotic, BH3-only protein BIM in serial biopsy samples. Therefore, we hypothesize that the combination of PLX-4720 (Vem analog) with navitoclax will result in increased anti-tumor activity. To test our hypothesis, we performed cell viability studies, Annexin:PI and ELISA apoptosis assays in addition to protein and mRNA analysis. In-vivo studies were performed in two BRAF mutant xenograft models using navitoclax and PLX-4720. In-vitro, our cell viability studies demonstrated that concurrent treatment with PLX-4720 and navitoclax results in an additive viability reduction in BRAF mutant but not in BRAF WT cell lines. The decrease in cell viability correlated to downmodulation of MCL-1 and BIM induction after PLX-4720 treatment, with further enhancement of BIM expression and PARP cleavage after adding navitoclax. In vivo, the navitoclax enhanced the efficacy of PLX-4720 in both xenograft models. The combination of a selective BRAF inhibitor with a BH3-mimetic may be a promising therapeutic strategy to enhance the clinical efficacy of BRAF inhibitors. Citation Format: Dennie T. Frederick, Roberto A. Salas Fragomeni, Taylor Hoff, Zachary A. Cooper, James W. Mier, Jennifer A. Wargo, Ryan J. Sullivan. BRAF inhibition is enhanced by BH3-mimetic through BIM induction. [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 1724. doi:10.1158/1538-7445.AM2013-1724
DDT and Breast Cancer: The Verdict Isn't In
Authors: L. F. Anderson
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article DDT and Breast Cancer: The Verdict Isn't In Get access Linda F. Anderson Linda F. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 8, 20 April 1994, Pages 576–577, https://doi.org/10.1093/jnci/86.8.576 Published: 20 April 1994
FRI0418 Case-mix in a rheumatology outpatient department of a london teaching hospital
Authors: B. Kirkpatrick, D. Ludwig, D. Pyne, S. Kelly
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> As a result of mounting financial pressures in the UK National Health Service, Rheumatology outpatient departments are under pressure from commissioning groups to adhere to pre-defined "new-to-follow-up" (N:FU) patient ratios. However, with many rheumatology patients requiring regular follow-up due to the nature of both their chronic condition and their treatment it appears that low new-to-follow-up target ratios could be difficult to meet. <h3>Objectives</h3> In the East End of London a target N:FU ratio of 1:4 has recently been commissioned. We aimed to study the patient case-mix in the Rheumatology outpatient department at The Royal London Hospital in East London to determine the feasibility of complying with this target. <h3>Methods</h3> Information was collected retrospectively over a 4 week period in November 2011 from all rheumatology consultant - led clinic lists at the Royal London Hospital. Clinic letters were used to determine diagnosis and treatment. <h3>Results</h3> 1148 outpatients were seen over the 4 week period. Mean patient age was 51.The overall N:FU ratio was 7.2. The majority of patients had chronic conditions: 42% (n=478) had Inflammatory Arthritis (IA) of which rheumatoid arthritis was the commonest (21%, n=238) followed by psoriatic arthritis (7%, n=86), then ankylosing spondylitis (5%, n=60); 14% (n=162) had a connective tissue disease (CTD) of which lupus was the commonest (7%, n=81). Within the IA and CTD groups 71% (n=339) and 63% (n=101) respectively were on immunosuppressant drugs which required specialist follow up. The remaining patients had soft tissue disorders, which included back pain (5%, n=61), metabolic bone disorders (6%, n=71), osteoarthritis (9%, n=104), unknown (6%, n=73) and other (7%, n=85) e.g. sarcoidosis and chronic pain syndrome. <h3>Conclusions</h3> Around 60% of the outpatient work-load of the Rheumatology Department is dealing with IA or CTDs - these are patients with chronic diseases, the majority of whom are on specialist drugs, and who cannot therefore be easily discharged back into the community. Soft tissue disorders and osteoarthritis which are mainly managed in the community make up a much smaller percentage of hospital work. We would therefore urge commissioners that in making decisions regarding appropriate N:FU ratios for outpatients consideration be taken of the current case-mix in rheumatology units. <h3>Disclosure of Interest</h3> None Declared
THU0348 Cost-Effectiveness of Physical Therapy Program in Cervical Intervertebral Disc Herniation
Authors: Ö.F. Sapmaz, D. Evcik, S. Ay, S. Koldaş Doğan, S. Yüksel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Neck pain is a common health problem and is quite important because of high costs due to direct and indirect economic losts for the community [1,2] <h3>Objectives</h3> The aim of this study is to compare cost-effectiveness of inpatient and outpatient physical therapy programs for patients with cervical intervertebral disc herniation. <h3>Methods</h3> Fifty nine patients with cervical intervertebral disc herniation diagnosed based on physical examination and Magnetic Resonance Imaging were included in the study. Patients were divided into two groups. Group 1 (n=30) received inpatient physical therapy program (electrotherapy, superficial-deep heat administration and basic cervical exercise program), and group 2 (n=29) received outpatient physical therapy program (the same treatment schedule. Assessment parameters were pain, functional capacity and quality of life (QoL). Patients9 global assesment and doctor9s global assessment were also measured. Pain intensity, patients9 - doctor9s global assessment were measured with visual analog scale (VAS). Functional capacity was assesed with neck disability index and QoL with short form 36 (SF-36). The expenses spent were calculated as direct health, direct non-health and indirect costs. All expenditures and all measurements were assessed for five times during the entire study: before treatment, just after treatment, and after first, third and sixth months of the treatment. <h3>Results</h3> In our study, we found that out-patient treatment had the the lowest cost compared to inpatient group. The estimated total costs for 6 months of out-patient and in-patient treatments were 3.058,99 TL (approximately 1.016,27 EUR) and 4.938,00 TL (approximately 1.640,53 EUR) respectively. Total utilities of these treatments were 0.69 and 0.72 respectively. An additional 1.897,01 TL (approximately 630 EUR) per one patient were gained compaired to inpatient treatment <h3>Conclusions</h3> This study suggested that physical therapy programs were effective in the treatment of pain and functional capacity in cervical intervertebral disc herniation patients. However, inpatient physical therapy program was found to have higher cost and more effective than outpatient physical therapy program <h3>References</h3> Wohns R.Surg Neurol.Int. 2010;1:77 Safety and cost-effectiveness of outpatient cervical disc artroplasty Kızıl, R Turkiye Klinikleri J PM&amp;R-Special Topics 2009;2(3):35-43 Servikal Disk Hernileri <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1925
Case 39-2001
Authors: A Sadeghi-Nejad, F M Graeme-Cook
Journal: New England Journal of Medicine (2001)

Presentation of CaseA two-day-old girl was admitted to the hospital because of persistent hypoglycemia.The infant had been born at 34 weeks' gestation to a 35-year-old mother after an uneventful pregnancy. The birth weight was 3510 g. The Apgar score was 4 at one minute and 7 at five minutes. There was no maternal history of gestational or insulin-dependent diabetes mellitus. The blood glucose level, measured at the hospital where the child was born, was less than 10 mg per deciliter (0.6 mmol per liter). An umbilical arterial catheter was inserted, and a bolus of glucose was given, followed . . .