tbuckley/cabot-search huggingface dataset:
Abstract 2425: Mechanisms of neuroblastoma metastasis to bone
Authors: Larry Carter, Courtney Varin, Cynthia M. van Golen
Journal: Cancer Research (2011)

Abstract The molecular pathways leading to neuroblastoma (NBL) development and progression are understudied despite the fact this tumor is responsible for 15% of all childhood cancer deaths. Bone is one of the most common sites of metastasis in NBL, and over 90% of children with NBL bone metastasis will die. Therefore, the goal of this study is to elucidate the cell-signaling pathways responsible for the destruction of bone. Parathyroid hormone related protein (PTHrP) and Transforming Growth Factor Beta both are involved in osteoclastogenesis. PTHrP travels through the circulation to the bones, where it triggers a chain of event that encourages the dissolution of bone minerals by osteoclast. Moreover, PTHrP results in the mobilization of calcium ions, which travel back via the circulatory system allowing osteoclast differentiation to go unchecked, therefore providing further destruction to the bone microenvironment. Transforming Growth Factor Beta (TGF-β) is a protein which controls proliferation, cellular differentiation and other functions in most cells. Since TGF-β and the SMAD family of proteins modulate the activity TGF-β and its association with osteoclasts, we formulated the hypothesis that osteoclastogenesis occurs during NBL bone metastasis through PTHrP and TGF-β. NBL is a heterogeneous tumor consisting of neuronal (n) and stromal (s) cells, with metastatic cells predominantly of the n type. In our study, we focused on four NBL cell lines: IMR-32 (n), SH-SY5Y (n), SK-N-AS (s), SK-N-SH (s). Conditioned media collected from IMR32 NBL cells induces osteoclast precursors to fuse into multinucleated, TRAP positive cells, indicative of osteoclast differentiation. Whole cell lysates were collected and Western immunoblotting performed for PTHrP. We report that the more tumorigenic cells, SH-SY5Y and IMR32, express higher levels of PTHrP than the s lines SK-N-AS and SK-N-SH. These data indicate that PTHrP may be involved in NBL bone metastasis. We are currently analyzing the effects of TGF-β on NBL and the role of these proteins in NBL-induced osteoclastogenesis. 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 2425. doi:10.1158/1538-7445.AM2011-2425
AB0365 Sleep Disorders in Moroccan Patients with Rheumatoid Arthritis
Authors: T. Lakhdar, F. Allali, L. Medrare, S. El Kabbaj, I. Ben Slama, A. Ngeuleu, H. Rkain, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> This study aimed to evaluate the frequency of sleep disorders in patients with rheumatoid arthritis (RA) and to explore the determinants of these disorders. <h3>Methods</h3> It is a cross-sectional study including patients with RA. Patients with a known psychiatric disorder were excluded from the study. The demographic characteristics of patients and the characteristics of RA were collected. Pain and fatigue were assessed by a visual analogue scale (0-100 mm), the disease activity by DAS28 - ESR (Disease Activity Score), the Functional Disability by the Arabic validated version of the Health Assessment Questionnaire (HAQ), the quality of life by Euroqol 5D and psychological state by the Arabic validated version of the questionnaire Hospital Anxiety and Depression (HAD) with its two items anxiety and depression. Participants completed the self-rated questionnaire “Pittsburgh Sleep Quality Index (PSQI)” that assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven “component” scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The total score ranges from 0 (no disorder) and 21 (major problems) <sup>1</sup>. Univariate and multivariate linear regression was performed to determine factors associated with poor sleep quality. <h3>Results</h3> 103 patients were included with a mean age of 49.7±11.4 years and a female predominance (90 (87.4%)). The median of RA duration was 8.16 years [3.25 to 14.16]. The median of global score PSQI was 5 [2-9]. Poorer Sleep quality was significantly associated with high disease activity (r =0.381, 95% CI [0.465, 1.320], p&lt;0.001), lower quality of life (r = -0.327, 95% CI [-5.396 - 1.474], p=0.001), greater functional disability (r =0.289, 95% CI [ 0.323, 1.539], p=0.003), greater pain severity VAS (r =0.350, 95% CI [0.023, 0.075], p&lt;0.001), increased fatigue VAS (r =0.380, 95% CI [0.030, 0.084], p&lt;0.001), higher levels of anxiety (r =0.385, 95% CI [0.178, 0.498], p&lt;0.001) and depression (r =0.310, 95% CI [0.103, 0.417]. In multivariate analysis, sleep disorders were associated with only higher levels of anxiety (r =0.254, 95% CI [0.033, 0.413], p=0.022). <h3>Conclusions</h3> Our study suggests that sleep disorders, in rheumatoid arthritis, are more frequently found in patients with associated anxiety disorders. <h3>References</h3> Sleep Quality and Functional Disability in Patients with Rheumatoid Arthritis; FS Luyster, ER Chasens, MCM Wasko et al; Journal of Clinical Sleep Medicine, Vol. 7, No. 1, 2011 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4772
Use of Tc-99m HMPAO Leukocyte Scans To Evaluate Bone Infection
Authors: Y C Weon, S O Yang, Y Y Choi, J W Shin, J S Ryu, M J Shin, S H Lee, H K Lee
Journal: Clinical Nuclear Medicine (2000)

In this study, the diagnostic value of Tc-99m hexamethylpropylene amine oxime (HMPAO) leukocyte scans and the role of additional SPECT in the diagnosis of bone infection were evaluated.The Tc-99m HMPAO leukocyte scans of 37 patients with clinically suspected bone infection were reviewed. The patients were divided into two groups according to the presence of orthopedic implants. Early (4 to 6 hours) and delayed (18 to 20 hours) planar images and early SPECT images were obtained. The final diagnosis of infection was made based on the pathologic, bacteriologic, and surgical data and clinical follow-up.Group 1 (25 patients with orthopedic implants) included 15 true-positive, 1 false-negative, 7 true-negative, and 2 false-positive results. Group 2 (12 patients without orthopedic implants) included 7 true-positive, 1 false-negative, and 4 true-negative results. The overall sensitivity of the Tc-99m HMPAO leukocyte scan with SPECT to detect bone infection was 92%, with a specificity rate of 85%. (Group 1: sensitivity, 94%; specificity, 78%. Group 2: 88% and 100% sensitivity and specificity, respectively.)The Tc-99m HMPAO leukocyte scan is useful in the diagnosis of bone infection, regardless of the presence of orthopedic implants. The additional SPECT images may be helpful to localize the site of infection more accurately.
Is there consensus in the definition of endpoints in metastatic breast cancer?.
Authors: ED Saad, A Katz
Journal: Cancer Research (2009)

Abstract Abstract #3102 Objective: Progression-free survival (PFS) is defined as the time between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. Time to tumor progression (TTP) is theoretically different from PFS in that the event of interest is only disease progression. Both PFS and TTP have been considered as appropriate endpoints in drug development, but the extent to which investigators agree on their definition is unknown. We therefore assessed the recent literature regarding the consistence of the definition of PFS and TTP when used as primary endpoints in advanced breast cancer.&amp;#x2028; Methods: We searched PubMed using the medical subject headings “breast neoplasms” and “drug therapy”, limiting the search to phase III trials on systemic antineoplastic therapies published between January 1, 2000, and December 31, 2007 in one of ten leading medical journals in the field (Annals of Oncology, Breast Cancer Research and Treatment, British Journal of Cancer, Cancer, European Journal of Cancer, Journal of Clinical Oncology, Journal of the National Cancer Institute, Lancet Oncology, The Lancet and The New England Journal of Medicine). We excluded randomized phase II trials, factorial trials, studies on high-dose chemotherapy, papers reporting combined analyses of two or more separate trials, and companion studies on correlative biology or prognostic factors.&amp;#x2028; Results: The search yielded 59 trials enrolling a total of 23,371 evaluable patients in 122 treatment arms. PFS was the primary endpoint in 14 cases, and TTP in 21 when all treatment lines and modalities were considered (response rate was used in 20 cases, and overall survival in only one). For first-line chemotherapy trials (N=24), PFS and TTP were used as primary endpoints in 5 and 7 cases, respectively. In 5 of the 21 trials using TTP as the primary endpoint, no definition of this endpoint was reported in the article. Analysis of the other 16 cases showed that progressive disease was always considered an event in TTP analysis. However, in 13 of these cases, death (either from breast cancer or from any cause) was also counted as an event. The definition of PFS was reported in the article in 13 of the 14 trials using this primary endpoint. In all cases, the events of interest in Kaplan-Meier analyses included both progressive disease and death. In some cases, both terms (PFS and TTP) were even used to denote the same endpoint in the same paper.&amp;#x2028; Conclusion: Our review suggests that investigators are frequently using PFS and TTP interchangeably in metastatic breast cancer. Such use of terms may lead to confusion when results of different trials are evaluated in perspective, and standardization of the definitions seems therefore in order. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3102.
EVALUACIÓN DE LA SEGURIDAD Y EFICACIA DE LA POLIPECTOMÍA ENDOSCÓPICA DE PÓLIPOS DIFÍCILES (PD)
Authors: MH Núñez Rodríguez, P Díez-Redondo, P Gil-Simón, R Ruiz-Zorrilla, L Sancho del Val, J Barrio Andrés, C De la Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2012)

Introducción: No está clara la frecuencia con la que se derivan a cirugía en la práctica los PD en la actualidad. Objetivo: Evaluar la seguridad, eficacia y complicaciones de la resección endoscópica de pólipos “difíciles”. Material y método: Revisión de polipectomías de PD realizadas en un centro de referencia durante 18 meses (enero 2011-junio 2012). Se han considerado PD un tamaño >20mm más la impresión subjetiva de dificultad basada en morfología y/o localización. Hubo13 polipectomías del propio centro y 23 PD remitidos de otros hospitales. Resultados: 36 polipectomías en 35 pacientes (19 varones, 16 mujeres) edad mediana 64,5 años (40–84). Localización: recto 25%, sigma 33%, izquierdo 11%, hepático 6%, derecho 14% y ciego 11%. Tamaño medio 40mm (20–80mm). 18pólipos planos, 9 pediculados y 9sésiles. Técnica de resección mucosa endoscópica en bloque en 13pólipos y piecemeal en 23. Los pólipos planos se resecaron previa inyección submucosa en 13/18, fulguración: 7/18, resección tipo piecemeal: 16/18 y en bloque 2/18. Los pólipos pediculados se han resecado previa colocación de lazo: 7/9 y hemoclip: 5/9. Los pólipos sésiles se resecaron previa inyección submucosa en el 100%, fulguración 4/9, hemoclip: 3/9. Se utilizó endoscopio de visión lateral en: 2pólipos de ciego y un pólipo en sigma y gastroscopio en 17 de rectosigma (retroflexión en 15). Anatomía patológica: displasia leve 2/33, moderada 16/33, severa: 4/33, carcinomas in situ 8/33 (tratamiento quirúrgico en un caso) y adenocarcinomas 2/33 (derivados a cirugía). Seguimiento medio: 4 meses (1–18). Un caso de recidiva. Complicaciones: 2síndromes post-polipectomía y 3 hemorragias durante la resección endoscópica controladas con hemoclip. Conclusiones: La resección endoscópica es un tratamiento eficaz y aplicable a todos los PD, por lo que la indicación quirúrgica puede restringirse a los que cumplan criterios histológicos y evitarse en los demás. Las complicaciones no son diferentes a las de una polipectomía convencional siendo posible el tratamiento endoscópico.
Abstract 1739: Reversal of ABCB1- and ABCG2-mediated drug resistance by sildenafil
Authors: Amit K. Tiwari, Zhi Shi, Suneet Shukla, Robert W. Robey, Satyakam Singh, In-Wha Kim, Susan E. Bates, Xing-xiang Peng, Ioana Abraham, Suresh V. Ambudkar, Tanaji T. Talele, Li-wu Fu, Zhe-Sheng Chen
Journal: Cancer Research (2011)

Abstract Sildenafil is a selective inhibitor of type 5 cGMP-specific phosphodiesterase and is clinically used to treat erectile dysfunction and pulmonary arterial hypertension. Overexpression of ABC transporters such as ABCB1, ABCC1 and ABCG2 is one of the main causes of the development of resistance in cancer cells to chemotherapeutic drugs. However, the effect of sildenafil on these ABC transporters is still unknown. In the present study, we found that sildenafil had differential effects on these transporters. In ABCB1-overexpressing cells, non-toxic doses of sildenafil were found to inhibit resistance to ABCB1 substrate anticancer drugs, as well as significantly increase intracellular accumulation of [3H]-paclitaxel. Similarly, in ABCG2-overexpressing cells, sildenafil partially reversed resistance to ABCG2 substrate anticancer drugs and increased intracellular accumulation of [3H]-mitoxantrone as well as the fluorescent compound BODIPY-prazosin. Sildenafil also moderately inhibited the transport of [3H]-E217βG and [3H]-methotrexate by ABCG2. Sildenafil significantly stimulated ABCB1 ATPase activity but it only slightly stimulated ABCG2 ATPase activity. However, it inhibited photolabeling of both ABCB1 and ABCG2 with [125I]-IAAP. Additionally, sildenafil did not alter the sensitivity of parental, ABCB1- or ABCG2-overexpressing cells to non-ABCB1 and non-ABCG2 substrate drug and had no effect on the function of ABCC1. We also modeled the binding of sildenafil within the large cavity of the transmembrane region of homology model of ABCB1 based on the mouse Abcb1a structure. Overall, we conclude that sildenafil can inhibit the function of ABCB1 and ABCG2, with a stronger effect on ABCB1. These findings suggest that it may be possible to develop potent MDR reversal agents from clinically approved drugs with known side effects and drug interactions. 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 1739. doi:10.1158/1538-7445.AM2011-1739
Can Hybrid SPECT-CT Overcome the Limitations Associated With Poor Imaging Properties of 131I-MIBG?
Authors: Punit Sharma, Varun Singh Dhull, Sunil Jeph, Rama Mohan Reddy, Harmandeep Singh, Niraj Naswa, Chandrasekhar Bal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2013)

This study aimed to evaluate the incremental value of (131)I-MIBG hybrid SPECT-CT over planar scintigraphy (PS) and SPECT alone in patients with clinical or biochemical suspicion of pheochromocytoma.A total of 126 adrenals of 63 patients (mean [SD] age, 28.6 [15.7] years; male patients, n = 34; female patients, n = 29) with clinical or biochemical suspicion of pheochromocytoma were retrospectively evaluated. All patients had undergone (131)I-MIBG SPECT-CT of adrenal region. The PS, SPECT, and SPECT-CT images were independently evaluated by 2 nuclear medicine physicians with 6 years (R1) and 2 years (R2) experience and in separate sessions 1 week apart. A scoring scale of 1 to 5 was used, in which 1 is definitely abnormal, 2 is probably abnormal, 3 is indeterminate, 4 is probably normal, and 5 is definitely normal. Sensitivity, specificity, predictive values were calculated taking a score 2 or less as abnormal. With receiver operating characteristic (ROC) curve analysis, areas under the curve (AUC) were calculated for each modality and compared. Histopathology and/or clinical/imaging follow-up were taken as reference standard.Of the 126 adrenals evaluated, 29 were indeterminate on PS for R1 and 48 for R2, 39 were indeterminate on SPECT for both, and on SPECT-CT, 1 was indeterminate for R1 and 2 for R2. SPECT-CT correctly characterized 28 of 29 indeterminate adrenals on PS and 37 of 39 indeterminate adrenals on SPECT for R1. Similarly, for R2, SPECT-CT correctly characterized 45 of 48 indeterminate adrenals on PS and 33 of 39 indeterminate adrenals on SPECT. On ROC comparison, PS was inferior to SPECT (P = 0.040 for R1; P < 0.001 for R2) and SPECT-CT (P = 0.001 for R1; P < 0.001 for R2) for both the observers. Moreover, SPECT was inferior to SPECT-CT for both the observers (P = 0.017 for R1 and P = 0.001 for R2). Accuracy of SPECT-CT (R1, 97.6%; R2, 97.6%) was higher than PS (R1, 91.2%; R2, 84.1%) and SPECT (R1, 94.4%; R2, 86.5%). Interobserver agreement was highest for SPECT-CT (κ = 0.966) as compared with PS (κ = 0.815) and SPECT (κ = 0.826).I-MIBG hybrid SPECT-CT shows high sensitivity and specificity for characterizing adrenal lesions in patients with clinical or biochemical suspicion of pheochromocytoma and is superior to PS and SPECT alone. It will be especially useful in countries where (123)I-MIBG is not available.
Percutaneous endoscopic gastrostomy placement during pregnancy in the critical care setting
Authors: V. Senadhi, J. Chaudhary, S. Dutta
Journal: Endoscopy (2010)

A 37-year-old woman with a past medical history of untreated hypertension presented with unresponsiveness at 28 weeks of gestation. Computed tomography (CT) revealed a pontine hemorrhage with massive edema. After 2 weeks of nasogastric feeding, the patient received a percutaneous endoscopic gastrostomy (PEG) tube. At 31 weeks, cesarean section was performed and a 1660-g preterm infant was delivered. The patient continued on PEG feeding and slight neurological improvement was seen.
Evaluation de l'extraction d'une prothèse plastique expansible couverte (SEPS) après radio-chimiothérapie pour cancer avancé de l'oesophage
Authors: A Laquière, D Heresbach, F Prat, JP Arpurt, P Bichard, J Berthillier, M Gaudric, PN d'Halluin, C Boustière, R Laugier
Journal: Endoscopy (2012)

Les patients présentant un cancer avancé de l'oesophage ont fréquemment une dysphagie importante ne régressant qu'à la fin de la Radio-Chimiothérapie (RC). Le traitement précoce de la dysphagie par une prothèse oesophagienne mise en place avant le début de la RC pourrait améliorer la dysphagie et la qualité de vie des patients. Le retrait de la prothèse après la fin de la RC est primordial pour les patients en réponse complète ainsi que pour le bilan d'évaluation. L'objectif principal de l'étude était d'évaluer l'extraction d'une SEPS à la fin de la RC. Les objectifs secondaires étaient l'étude de l'efficacité et de la tolérance de cette prothèse.
Three-day regimen of fluorouracil and cisplatin combination chemotherapy for persistence, metastatic or recurrent uterine cervical cancer
Authors: M. Lee., H. Yi, E. Song, M. Im, J. Im, B. Lee, C. Kim
Journal: Journal of Clinical Oncology (2006)

15049 Background: The five-day infusion of FP(5-fluorouracil, cisplatin) combination therapy is one of the most popular regimens for advanced cervical cancer, which has yield a 50∼60% response rate. There is some variance in the FP combination, for example, longer infusion of FP requiring longer hospitalization as well as causing more discomfort to the patients. This study was designed to assess the therapeutic effect and toxicities of three day regimen of FP combination chemotherapy instead of five day regimen for disseminated or recurrent cervical cancer. Methods: From July 1996 through April 2001, 39 patients with advanced or recurrent cervical cancer were enrolled in the study. The regimen consisted of continuous 12-hour infusion of 5-FU(5-fluorouracil) at 1000 mg/m 2 /day plus bolus infusion of cisplatin at 25mg/m 2 /day for 3 days. The treatment was repeated every 3 weeks. Results: Thirty five patients with a median age of 53 years were evaluable for response during the median follow up of 21.5 months. The response rate was 45.7% (4 CR and 12 PR), and the median duration of the overall survival was 45 months. Toxicity was acceptable with no treatment related mortality. Neutropenia in grade 3 or more was seen in 16% with 4 febrile episodes throughout a total 232 cycles. It did not appear alopecia and gastointestinal trouble in grade 3 or more. Conclusions: These results revealed that the toxicity of 3 day regimen of 5-FU and cisplatin is acceptable and the efficacy comparable to that of 5 day regimen. No significant financial relationships to disclose.
Informed Consent — Why Are Its Goals Imperfectly Realized?
Authors: Barrie R. Cassileth, Robert V. Zupkis, Katherine Sutton-Smith, Vicki March
Journal: New England Journal of Medicine (1980)

Abstract We explored reasons for the failure of patients to recall major portions of the information on consent forms and in oral explanations about consent. Within one day of signing consent forms for chemotherapy, radiation therapy, or surgery, 200 cancer patients completed a test of their recall of the material in the consent explanation and filled out a questionnaire regarding their opinions of its purpose, content, and implications. Only 60 per cent understood the purpose and nature of the procedure, and only 55 per cent correctly listed even one major risk or complication. We found that three factors were related to inadequate recall: education, medical status, and the care with which patients thought they had read their consent forms before signing. Only 40 per cent of the patients had read the form "carefully." Most believed that consent forms were meant to "protect the physician's rights." Although most thought that consent forms were necessary and comprehensible and that they contained worthwhile information, the legalistic connotations of the forms appeared to lead to cursory reading and inadequate recall. (N Engl J Med. 1980; 302:896–900.)
Purification of a Gelatin-Degrading Type IV Collagenase Secreted by ras Oncogene-Transformed Fibroblasts
Authors: C. Spinucci, S. Zucker, J. M. Wieman, R. M. Lysik, B. Imhof, N. Ramamurthy, L. A. Liotta, H. Nagase
Journal: JNCI Journal of the National Cancer Institute (1988)

Connective tissue matrix-degrading metalloproteinases play an important role in cancer invasion. In this report we describe the isolation of a metalloproteinase exhibiting both type IV collagenolytic and gelatinolytic activities from the conditioned medium of NIH-3T3 fibroblasts transformed with DNA containing an activated c-Harvey-ras oncogene from T24 bladder cancer cells. This tumor proteinase was purified by anion exchange chromatography, zinc-chelate Sepharose chromatography, and gel permeation chromatography. The final product was homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (relative molecular mass = 67,000). Gelatin zymography revealed two bands of gelatinolytic activity, corresponding to molecular weights of 67,000 and 62,000. Upon immunoblotting with the use of an affinity-purified polyclonal rabbit antibody to a peptide region of type IV collagenase that lacks homology with interstitial collagenase or stromelysin, the purified tumor enzyme was identified as type IV collagenase.
Fifty Years Later: The Significance of the Nuremberg Code
Authors: Evelyne Shuster
Journal: New England Journal of Medicine (1997)

The Nuremberg Code 1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by . . .