tbuckley/cabot-search huggingface dataset:
Abstract 1530: Modulation of drug transporter expression in pancreatic cancer cells by indole-3-carbinol and gemcitabine: Potential transporter-targeted therapy
Authors: Beverly D. Lyn-Cook, Cornelius Davis, Kenneth Wiley, Beverly Word, George Hammons
Journal: Cancer Research (2010)

Abstract Increased expression of drug transporters that induces multidrug resistance is a critical event in poor prognosis and treatment for numerous cancers, particularly pancreatic cancer. Due to its aggressive and resistance characteristics, prognosis is often fatal. Recently, investigators have focused on the use of inhibitors of proteins transcribed by various drug transporters as a potential target for improved therapy of various chemotherapeutics. Gemcitabine is the current treatment for pancreatic cancer, although some patients respond poorly to the treatment. Interindividual differences in expression of drug transporters relating to drug resistance has been a major factor in different drug outcomes. In the present study, pancreatic cancer cells (Panc-1 and SU86. 86) showed expression of the following drug transporters, ABCB1, ABCA5, MRP5, SLCO1B1, and SLC5A6. Gemcitabine treatment alone down-regulated expression of ABCA5, SLCO1B1, and SLC5A6 (P&amp;lt;0.05) transporters. Gemcitabine (0.1 µM) or I3C (100 µM) alone had no effect on ABCB1 expression. However, combination of gemcitabine (0.1µM) and indole-3-carbinol(100 µM) significantly down-regulated ABCB1. ABCB1 codes for the multidrug protein, pgp. This combination significantly inhibited growth of pancreatic cancer cells by 70%. Gemcitabine and indole-3 carbinol also decreased expression of MRP5 expression. These data suggest that dietary agents in combination with chemotherapeutics are potential inhibitors of multidrug resistance by down-regulating these proteins thus allowing for increased efficacy of the drug for treatment of the cancer. 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 1530.
THU0330 Pulmonary Function and Computed Tomography Imaging in Primary SjöGren’s Syndrome and Risk Factors for Lung Complication in a Large Cohort
Authors: H. Gao, J. He, X.-W. Zhang, M. Feng, W. Zhao, Z.-G. Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary involvement is common in primary Sjögren's syndrome (pSS). Characteristics of pulmonary function and computed tomography imaging for pSS-associated lung disease which are feasible in clinic were less studied. In additon, there is limited information regarding the risk factors in the published literature dealing with pulmonary manifestations of pSS. <h3>Objectives</h3> We described the radiologic and pulmonary functional characteristics for pulmonary manifestation and detected the risk factors of lung involvement in a large cohort of pSS patients. <h3>Methods</h3> A total of 112 hospitalized patients with pSS-associated lung disease were retrospectively analyzed and recruited as study group. The high-resolution computed tomography (HRCT), pulmonary function test (PFT) and laboratory tests were evaluated. HRCT were re-evaluated by two experienced chest radiologists according to the classification of CT patterns described in the American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Seventy one patients without any organ damage were enrolled as control group to explore risk factors for lung involvement in pSS patients. <h3>Results</h3> Among the 112 pSS patients with lung involvement, 102 (91.10%) were female. The mean age was 61.74±10.24 years old. The disease duration was 60 months (12.00 to 147.00 months). <b>Results from descriptive study:</b> Lung involvement affected pulmonary lobes broadly, especially lower lobes. The total HRCT score was 9.71±4.77. The HRCT abnormalities involved many types, and the most frequent HRCT findings were linear opacities (94.2%) and ground-glass attenuation (87.0%). Impaired diffusing capacity was common (74.3%) and severe (predicted value of T<sub>LCO</sub> was 57.52±21.23%). Among the 36 patients taking artery blood gas (ABG), 20 patients had hypoxia and 7 had Type 1 respiratory failure. <b>Results from case control study:</b> Compared with the control group, the mean age and levels of RF, CRP, ESR were significant higher in study group, whereas, anti-SSA, anti-SSB and AFP were less common. Age and anti-SSA were retained as independent correlates after adjusting for all the factors with significant difference (P value for Age was 0.000; SSA 0.012). <h3>Conclusions</h3> Lung involvement is a severe complication for pSS patients. Age and anti-SSA are independent correlated with pulmonary complication in pSS patients. <h3>References</h3> Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathologic study. <i>Am J Respir Crit Care Med</i>. 2005; 171: 632-8. Yazisiz, V. et al. Lung involvement in patients with primary Sjogren's syndrome: what are the predictors? <i>Rheumatol Int</i> (2009). <h3>Disclosure of Interest</h3> None Declared
Abstract 5069: Genomic profiles of primary non-small cell lung cancer (NSCLC) xenograft tumors identify distinct gene signatures associated with histological subtypes
Authors: Christine To, Dan Strumpf, Devang Panchal, Ming Li, Nhu-An Pham, Wing Xie, Naoki Yanagawa, Bizhan Bandarchi, Michael Herman Chui, Sandy Der, Frances A. Shepherd, Thomas Kislinger, Michael Moran, Igor Jurisica, Lakshmi Muthuswamy, Ming-Sound Tsao
Journal: Cancer Research (2012)

Abstract Xenografts established directly from patient tumors mirror closely the histology of the primary tumors. Therefore, primary tumor xenografts (PTXG) may serve as important preclinical models to evaluate novel anti-cancer drugs. We previously reported that the ability of resected tumors to engraft in NOD-scid mice is a strong predictor of relapse after surgery and poorer prognosis in NSCLC patients, and thus may represent biologically more aggressive cancers (Clin Cancer Res 2011;17:134-41). Genomic characterization of PTXG would help identify genetic aberrations that drive malignant oncogenic pathways in NSCLC. We characterized the somatic copy number alterations (CNA) of 36 PTGX, consisting of 15 adenocarcinoma (ADC), 18 squamous cell carcinoma (SCC), 2 large cell neuroendocrine carcinoma (LCNEC) and 1 large cell carcinoma (LC), along with 34 patient normal samples as controls using Illumina Omni-1 Quad SNP arrays. The gene expression profiles of the 36 PTGX were analyzed using Illumina Omni-1 Quad HT-12 v4 arrays. Histology-specific recurrent regions of CNA observed in PTGX are concordant with the published and publicly available primary NSCLC CNAs. We identified 1053 genes with somatic copy number gains and 932 genes with somatic copy number losses that distinguish between SCC and ADC. From integrative analysis of mRNA expression and somatic CNAs, we identified 325 genes specific to ADC and 2232 specific to SCC that are well correlated. Gene candidates that are deregulated in ADC include WRN, STK35, SIX1; and genes that are over-expressed in SCC include SOX2, RNF13, WNK1, PIK3CA, TFRC, TP63, PAK2 suggesting there is differential deregulation of signaling pathways between these two subtypes of lung cancer. We have identified candidate gene signatures that distinguish between ADC and SCC from PTXG, suggesting these xenograft models can provide a valuable resource to study cancer biology and preclinical drug target evaluation in vivo. 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 5069. doi:1538-7445.AM2012-5069
Reversal of Medial Compartment Osteoarthritic Uptake Pattern After High Tibial Osteotomy
Authors: WARWICK BRUCE, SAM MACDESSI, HANS VAN DER WALL
Journal: Clinical Nuclear Medicine (2001)

Two cases of osteoarthritis of the knee are presented that illustrate the typical medial compartment pattern of scintigraphic uptake. In both cases the patients had significant medial joint pain. After high tibial osteotomy, the pattern of uptake was altered and paralleled the improvement in symptoms. These observations prompt several important issues regarding the cause of the uptake and may provide a way to monitor treatment response.
Abstract 1209: Next generation sequencing demonstrates multiple gene amplifications and mutations in 3 patients with estrogen receptor-positive breast cancer with responses to treatment with combination aromatase and PI3K/AKT/mTOR pathway inhibition.
Authors: Ralph Zinner, Johnique T. Atkins, Filip Janku, Stacy Moulder, Phil Stephens, Roman Yelensky, Robert Wolff, Razelle Kurzrock, Jennifer J. Wheler
Journal: Cancer Research (2013)

Abstract Background: Gene amplifications in breast cancer may indicate poor prognosis disease, particularly for patients with multiple amplifications. Endocrine response and resistance in breast cancer maybe revealed to PI3K/AKT/mTOR pathway activation. Patients and Methods: We analyzed tissue with next generation sequencing (NGS) from 3 patients with estrogen receptor (ER)-positive breast cancer treated on a dose escalation study with anastrozole, an aromatase inhibitor, and everolimus, an mTOR inhibitor. Genomic libraries were captured for 3230 exons in 182 cancer related genes plus 37 introns from 14 genes, often rearranged in cancer (Foundation Medicine, Cambridge, MA). Results: Twelve of 50 evaluable patients with ER-positive breast and gynecologic tumors treated with anastrozole (1mg PO daily) and everolimus (either 5mg PO daily or 10mg PO daily) had SD ≥ 6 months/PR/CR. NGS analysis on 3 of the 12 patients tumors demonstrated multiple amplifications, including: CCND1, CCNE1, FGFR1, MYC, IRS2 and MCL1. One patient had a complete response (CR) and two patients achieved partial responses (PR) with an 80% decrease in disease in one patient and a 38% decrease in disease in the other. All 3 patients had ER-positive breast cancer and previously experienced progression of disease while receiving hormone therapy. These amplifications seen have all been linked to hormone therapy resistance in ER-positive breast cancers. Two of these patients also had direct alterations in the PI3K/AKT/mTOR pathway: PIK3CA and PIK3R1 mutations in one patient and PTEN loss in another. Conclusions: Molecular profiling of 3 patients with ER-positive breast cancer with PR/CR on treatment with anastrozole/everolimus revealed multiple genetic alterations. Among these alterations were amplifications that may be associated with resistance to hormone therapies. Further exploration of combination hormonal therapies and correlative molecular profiling is warranted. Citation Format: Ralph Zinner, Johnique T. Atkins, Filip Janku, Stacy Moulder, Phil Stephens, Roman Yelensky, Robert Wolff, Razelle Kurzrock, Jennifer J. Wheler. Next generation sequencing demonstrates multiple gene amplifications and mutations in 3 patients with estrogen receptor-positive breast cancer with responses to treatment with combination aromatase and PI3K/AKT/mTOR pathway inhibition. [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 1209. doi:10.1158/1538-7445.AM2013-1209
Inhibition of Corticosteroid Secretion by Amphenone in a Patient with Adrenocortical Carcinoma
Authors: George W. Thorn, Albert E. Renold, Alan Goldfien, Don H. Nelson, William J. Reddy, Roy Hertz
Journal: New England Journal of Medicine (1956)

AMPHENONE was synthesized in 1950 by Allen and Corwin1 as one of a series of substituted desoxybenzoins and was selected by Hertz and his collaborators2 , 3 as a compound of potential biologic interest because of its structural relation to synthetic estrogens. These investigators found that the substance exerted progestational activity in the rabbit, and a partly progestational, partly estrogenic activity in the rat. In addition, amphenone was shown to produce enlargement of both the adrenal and the thyroid glands. Later studies concerned primarily the nature of the adrenal enlargement and it was suggested that amphenone interfered with the production of active . . .
Prenatal Treatment of Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Songya Pang, Marilyn S. Pollack, Robert N. Marshall, LaDonna Immken
Journal: New England Journal of Medicine (1990)

CONGENITAL adrenal hyperplasia due to 21-hydroxylase deficiency is the most common cause of female pseudohermaphroditism. The severe classic disorder results in excess adrenal secretion of androgen from early fetal life, thereby causing the virilization of the external genitalia of affected female fetuses from the time of sexual differentiation onward. In human fetuses, sexual differentiation is believed to occur between 9 and 13 weeks of gestation.1 , 2 We can thus presume that the increased secretion of androgen by the adrenals in fetuses with congenital adrenal hyperplasia begins during or even before this critical period.Congenital adrenal hyperplasia is an HLA-linked autosomal recessive . . .
Surgical-Wound Infection with<i>Pasteurella multocida</i>from Pet Dogs
Authors: Jackie Octavio, William Rosenberg, John E. Conte
Journal: New England Journal of Medicine (2001)

To the Editor: We describe a patient in whom a surgical-site infection probably developed from contact with his pet dogs. A 59-year-old man underwent posterior C1–C2 transarticular screw fixation and fusion for cervical instability. Five days after discharge, he was readmitted with an infection at the surgical site. Magnetic resonance imaging revealed a collection of fluid located in the posterior cervical area and extending to the epidural space. Emergency incision and drainage were performed; the procedure was complicated by a myocardial infarction, which required transfer to the intensive care unit. Blood cultures were positive for Pasteurella multocida, and culture of . . .
Case 33-2005
Authors: Joshua Korzenik, Daniel C. Chung, Subba Digumarthy, Kamran Badizadegan
Journal: New England Journal of Medicine (2005)

A 43-year-old man was admitted to the hospital because of acute rectal bleeding. He had had episodes of rectal bleeding intermittently since childhood, and numerous polyps had been resected from the colon, stomach, and duodenum. He also had frequent epistaxis, and vascular malformations had been detected in the nose and lungs. His mother had a similar history. Diagnostic tests were performed.
IMPACT OF ACUTE KIDNEY INJURY DURING INITIAL TREATMENT ON WORSE CLINICAL OUTCOME IN PATIENTS WITH ACUTE HEART FAILURE
Authors: Yoshiya Yamamoto, Toshiyuki Nagai, Yasuo Sugano, Tatsuhiro Shibata, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2015)
COMBINATION OF MITRAL VALVE TETHERING AND ANNULAR DILATATION AS A MECHANISM OF MITRAL REGURGITATION SECONDARY TO ATRIAL FIBRILLATION: SERIAL TRANSESOPHAGEAL ECHOCARDIOGRAPHIC STUDY AFTER RADIOFREQUENCY CATHETER ABLATION
Authors: Daimon Kuwahara, Nozomi Watanabe, Keiichi Ashikaga, Tomoko Fukuda, Shun Nishino, Hirohide Matsuura, Tatsuya Nakama, Makoto Furugen, Hiroshi Koiwaya, Nehiro Kuriyama, Yoshisato Shibata
Journal: Journal of the American College of Cardiology (2016)
AB0430 Effects of Abatacept and TNF Inhibitors Compared with Ultrasonography in Patients with Rheumatoid Arthritis
Authors: K. Mamoto, T. Koike, T. Okano, Y. Sugioka, M. Tada, K. Inui, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The present study aimed to compare the effects of abatacept (ABT) and tumor necrosis factor inhibitors (TNFi) against rheumatoid arthritis (RA). <h3>Methods</h3> Patients with RA were treated with ABT (n=51) or TNFi (n=89; adalimumab, n=35; etanercept n=23; infliximab n=15; golimumab n=16). Twenty-six synovial sites comprising 22 joints (bilateral first to fifth metacarpophalangeal (dorsal recess), first interphalangeal and second to fifth proximal interphalangeal (dorsal recess) joints and dorsal radial, dorsal median and dorsal ulnar parts of the wrists) were assessed by musculoskeletal ultrasonography. Gray scale and power Doppler signals in these joints were semi-quantified using a scale from 0 to 3. We then compared disease activity, 28-CRP (DAS) scores and the sum of GSUS and PDUS scores between the two groups. <h3>Results</h3> The DAS score was significantly lower after two months of TNFi treatment compared with baseline, but did not significantly improve compared with baseline in the ABT group at two months. The DAS scores were lower for the TNFi than for the ABT group at six and eight months, but did not significantly differ at 12 months (Fig. 1). The sums of the GSUS and PDUS scores at 12 months were lower than those at baseline in both groups; however, these differences were not significant. <h3>Conclusions</h3> The clinical effect of ABT was slower than that of TNFi, but matched those of TNFi at 12 months. The effects of ABT and TNFi were similar according to ultrasound assessment. <h3>Disclosure of Interest</h3> K. Mamoto: None declared, T. Koike Grant/research support: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, T. Okano: None declared, Y. Sugioka: None declared, M. Tada: None declared, K. Inui Grant/research support: Chugai Pharmaceutical Co., Ltd.,Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Abbvie GK, Eisai Co.,Ltd., MSD K.K. Speakers bureau: Bristol-Myers K.K., Takeda Pharmaceutical Corporation, Ltd., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.,Abbvie GK,Astellas Pharma Inc., H. Nakamura Grant/research support: Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Nippon Zoki Pharmaceutical Co., Ltd., Daiichi Sankyo Speakers bureau: Eisai Co.,Ltd., Daiichi Sankyo <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3222
What Happened to the “Panda” Sign?
Authors: Pareen Mehta
Journal: Clinical Nuclear Medicine (2016)

From the Departments of Radiology and Nuclear Medicine, Keck School of Medicine of USC, Los Angeles, CA. Received for publication December 9, 2015; revision accepted December 14, 2015. Conflicts of interest and sources of funding: none declared. Correspondence to: Pareen Mehta, MD, 1200 N, State St, D&T Bldg, Room 3D321, Los Angeles, CA 90033. E-mail: [email protected].
Atypical placement of the pylorus: a rare congenital abnormality
Authors: Turan Calhan, Abdurrahman Sahin, Resul Kahraman, Aziz Batu
Journal: Endoscopy (2014)

The most common congenital abnormality of the pylorus is hypertrophic pyloric stenosis, which occurs in about 3 in every 1000 live births and is an extremely rare disorder in adulthood [1] [2]. Other congenital abnormalities are less frequently seen; most of them present in infancy or childhood and cause gastric outlet obstruction [3] [4]. We present here the case of an older man who was found to have congenital displacement of the pylorus without any previous evidence of obstructive symptoms.
Abstract LB-38: Selective Smoothened antagonists for anti-tumor therapy
Authors: Patrizia Tunici, Mariateresa Mancuso, Cinzia Giordano, Pietro Ferruzzi, Federica Mennillo, Mirella Tanori, Anna Saran, Russell Thomas, Annette Bakker
Journal: Cancer Research (2011)

Abstract The Hedgehog (Hh) pathway is an important signaling pathway during cellular proliferation, differentiation and embryonic morphogenesis. Aberrant pathway activation has been linked to tumorigenesis in several cancers, (including pancreatic, prostate, lung, colorectal, bladder and ovarian) and therefore the inhibition of the pathway could be an attractive approach for anticancer therapy. The pathway is either activated by the binding of one of the three Hh ligands (sonic, Indian and desert) to the Patched transmembrane protein or by the mutation of inhibitory pathway components (e.g. Pached, SUFU,…). Pathway activation by ligand binding to Patched releases patched repression of the smoothened (Smo) receptor. Activated Smo initiates a cascade of events leading to the activation of transcription factors of the Gli family. Pathway activation by mutation has been reported in diseases such as medulloblastoma or basal cell carcinoma in which the Patched co-receptor is mutated, thereby functionally inactivated and unable to repress the Smo receptor. We report the characterization of a novel Smoothened receptor antagonist (SEN450), showing Hedgehog pathway specific activity in hedgehog responsive cellular models. Finally, we show a synergistic effect of SEN450 with temozolomide in a subcutaneous CD-1 nude mice xenograft of DBTRG-05MG neurospheres. Our data indicate that growing conditions can affect hedgehog responsive cells and that a combined therapy with temozolomide and hedgehog inhibitors could be helpful in the prevention/delay of GBM recurrence. Moreover, we have obtained extremely promising in vivo data using two compounds structurally related to SEN450 in a xenograft tumour model that have been generated from irradiated heterozygous Patched mice. In the current study, the Ptc+/− mice were used to generate a tumor model by transplanting medulloblatoma fragments subcutaneously in nude mice. Upon tumor development two Smo antagonists administered orally were tested in this model. Both compounds showed a significant reduction in tumor volume that was maintained over the entire dosing period. Histological examination showed very low mitotic index in treated tumors versus controls. The expression of the target gene Gli1 revealed a significant decrease of the gene expression in treated samples. The results corroborated the specificity of action of both molecules in targeting the Hh pathway always activated in this tumor model. Further investigation is in progress in order to verify the antitumor capacity of the compounds in other tumor models. 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 LB-38. doi:10.1158/1538-7445.AM2011-LB-38
Pulmonary Artery Sarcoma Detected on F-18 FDG PET/CT as Origin of Multiple Spinal Metastases
Authors: In Kook Chun, Jae Seon Eo, Jin Chul Paeng, Dong Wan Kim, June-Key Chung, Dong Soo Lee
Journal: Clinical Nuclear Medicine (2011)

A 67-year-old man with back pain was diagnosed as having multiple spinal metastases on MRI. On CT scan, only a filling defect in the right pulmonary artery was observed and suspected as venous thromboembolism. On F-18 fluorodeoxyglucose (FDG) PET/CT, intense hypermetabolism was observed in the right pulmonary artery in addition to the metastatic spine lesions. Biopsy confirmed the lesion as a primary pulmonary artery sarcoma (PAS), and the spine lesions as metastases of PAS. Although PAS is rare and its bone metastasis presenting initial symptom is extremely rare, FDG PET/CT is an effective diagnostic modality for PAS, not only in discrimination from venous thromboembolism, but also in workup of metastatic origin.