tbuckley/cabot-search huggingface dataset:
Abstract PD06-07: Sentinel Node Biopsy Alone for Node Positive Breast Cancer, Report from the American College of Surgeon's National Cancer Database, 1998-2007
Authors: K Yao, H Du, G Addie, DJ Winchester, E Barrera, N Jaskowiak, S Trocha, DP. Winchester
Journal: Cancer Research (2010)

Abstract Background: The decision to perform complete node dissection for a tumor positive sentinel node (SN) has become controversial especially in light of the results of a randomized trial of sentinel node biopsy alone for node positive disease. We report national trends in the United States of SN biopsy alone from 1998-2007 for node positive disease from the National Cancer Database (NCDB) of the American College of Surgeons. Patients and Methods: Utilizing the NCDB Participant User File we analyzed 994,883 patients diagnosed with invasive breast cancer from 1998 to 2007. Neoadjuvant cases and patients with clinically positive axillary nodes were excluded. All patients underwent breast surgery. After applying exclusion criteria, 104,548 SN tumor positive patients were identified. 15,643 (14.9%) patients underwent SN biopsy alone and 88,905 (85.1%) patients underwent SN biopsy followed by completion axillary node dissection. Cross tabulations with patient, tumor and hospital factors were performed. Results: Over the 10 year period, there was a statistically significant increase in the number of patients undergoing SN biopsy alone, with 488 (9%) in 1998, and 1798 (17%) in 2007 (P&amp;lt;0.001), and similar pattern was seen across age (all p&amp;lt;.0001), income (all p&amp;lt;.0001), census region (all p&amp;lt;.001), tumor stage (all p&amp;lt;.01), and facility type categories (all p&amp;lt;.0001). Overall there was a significant increase in the number of patients undergoing sentinel node biopsy alone according to age, with 756 (10.2%) for patients ages 30 to 40 versus 1368 (24.2%) for patients ages 80 to 90 (P&amp;lt;0.0001). 7,149 (15.3%) of patients in the highest income range had SN biopsy alone versus 1387 (13.8%) in the lowest income range (p=0.0002). There were significant differences according to the census region with the highest rate for SN alone in the Northeast region, 1263 (21%) and lowest in the Atlantic region, 2116 (12.8%) (26.5%) (P&amp;lt;0.001). There were significant differences in SN biopsy alone according to tumor stage, with 14441 (16.8%) Stage II patients had SN alone versus 577 (3.5%) for those with Stage III tumors (P&amp;lt;0.0001). There were minimal differences in the facility type, with 2090 (15%) patients treated at a community cancer program had SN alone versus 8646 (15%) at a comprehensive community cancer program versus 4907 (14%) at an academic/teaching program (p=0.501). Conclusions: The utilization of SN biopsy alone for patients with node positive breast cancer has significantly increased from 1998 to 2007. Patient age, tumor size, and socioeconomic status, were significant predictive variables but facility type was not. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-07.
Abstract 1198: Adaptation to ER stress as a driver of increased expression of Mcl-1 with melanoma progression
Authors: Chen Chen Jiang, Li Qing Zhuang, Li Dong, Rick Throne, Christopher Lavis, Peter Hersey, Xu Dong Zhang
Journal: Cancer Research (2010)

Abstract Past studies have shown that Mcl-1 expression increases with melanoma progression, which is an important mechanism of resistance of melanoma cells to apoptosis. We show here that up-regulation of Mcl-1 in melanoma is a consequence of adaptation of melanoma cells to endoplasmic reticulum (ER) stress. Exposure of cultured melanoma cells and fresh melanoma isolates to pharmacological ER stress inducers results in up-regulation of Bcl-2 and Mcl-1. Inhibition of Mcl-1 renders melanoma cells more sensitive to ER stress-induced apoptosis even when Bcl-2 is over-expressed, but inhibition of Bcl-2 does not increase the sensitivity to ER stress-induced apoptosis in melanoma cells over-expressing Mcl-1. Up-regulation of Mcl-1 by ER stress involves multiple mechanisms. The transcriptional increase is mediated by the transcription factor ETS-1 downstream of the XBP1 axis of the unfolded protein response, whereas down-regulation of GSK3α is responsible for reduced proteasomal degradation of Mcl-1 in melanoma cells under ER stress. Studies on a large cohort of melanocytic tumor tissue sections revealed that expression of GRP78, a classic marker of ER stress, and expression of LDH5, an indicator of hypoglycemia that is one of the causes of ER stress, correlate with Mcl-1 expression, indicating that the increase in Mcl-1 with melanoma progression in vivo is associated with ER stress. In addition, we demonstrate in this report that induction of apoptosis by ER stress in melanoma cells deficient in Mcl-1 is mediated by the BH3-only proteins PUMA and Noxa, whereas another BH3-only protein Bim does not appear to play a part in melanoma cells as it does in other cell types. In summary, our results indicate that adaptation to ER stress is a driver of up-regulation of Mcl-1 during progression of melanoma, and suggest that strategies aimed at inhibiting the activity of Mcl-1 may be important in the treatment of melanoma. 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 1198.
AB0528 Bone mineral density, vertebral fractures and their determinants in ankylosing spondylitis
Authors: M. Rossini, H. Mahamid, C. Caimmi, G. Orsolini, M. R. Povino, D. Gatti, O. Viapiana, E. Fracassi, A. Carletto, M. Biondan, S. Adami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoporosis responsible for loss of bone strength and vertebral fracture (VF) rates ranged from 0% to 18% have been reported in patients with ankylosing spondylitis (AS). <h3>Objectives</h3> In this study we examined the prevalence of low bone mineral density (BMD) and VF in patients with AS (modified New York criteria), and investigated the associations between BMD or VF and demographic, body composition or disease-related parameters. <h3>Methods</h3> Skeletal and body composition assessment included dual X-ray Absortiometry (DXA) at the lumbar spine, hip and total body and radiographs of the spine. The presence of VF was established by the Genant's semi-quantitative method. <h3>Results</h3> A total of 79 AS patients, 65 males and 14 females with mean age of 43 and 49 years, respectively and with a mean disease duration of 10 years were included. Mean Z score BMD (SD below the age- and gender-matched mean reference value) were slightly decreased only in male patients, both at lumbar spine and total hip (-0,4 p=0,05; -0,3 p&lt;0,01), while mean total body Z score BMD were positive in both genders (female +1,2 p&lt;0,05; male +0,7 p&lt;0,001), independent of the presence of syndesmophytes. Z score BMD values at both total hip and lumbar spine were directly and significantly (p&lt;0.01) associated with body mass index (BMI, Kg/m<sup>2</sup>); Z score BMD were significantly correlated with both fat and lean mass (kg), measured by DXA, only at hip sites. Z score BMD were significantly lower in the 36 patients with syndesmophytes and in those (19%) with peripheral joints involvement. Despite reasonably preserved BMD values at least one VF was identified in 31% of males and 14% of females; most VF were located at thoracic-lumbar transition and were mild wedge fractures. The presence of VF was not associated with BMD values (ANOVA) but rather with peripheral joints involvement (chi-square test, p&lt;0.01), Bath Ankylosing Spondylitis Metrology Index (logistic regression, p&lt;0,01), and Bath Ankylosing Spondylitis Functional Index (p&lt;0,01). <h3>Conclusions</h3> In this study we found that BMD is relatively well preserved in AS patients. The total body BMD values above the normal range suggest that the overall bone formation might be somewhat increased despite the propensity to decreased mobility. VF are very common particularly in male AS patients: its occurrence is unrelated with BMD values while it is significantly correlated with clinical parameters of disease activity and functional impairment. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-437: ICA-1: A novel PKC-i inhibitor inhibits the proliferation of prostate cancer cells
Authors: Aravind P. Bhayankara, Rekha Patel, Hla Win-Piazza, Prajit Pillai, Mildred E. Acevedo-Duncan
Journal: Cancer Research (2011)

Abstract Prostate cancers are highly lethal tumors and besides skin cancer, prostate cancer is the most common type of cancer among men in the United States. Approximately one third of men diagnosed with cancer each year will have prostate cancer. Certain prostate cancers are highly lethal tumors due to the emergence of therapy-resistant prostate cancer cells. PKC-iota (PKC-ι) is an oncogene and an atypical protein kinase C isoform that confers resistance to drug-induced apoptosis in cancer cells (J. Biol. Chem. 272; 44: 27521–27524). PKC is of special interest since it is overexpressed in prostate cancers (Proc Natl Acad Sci U S A. 106:16369–16374). The objective of the study was to investigate the effects of inhibiting PKC-ι on the proliferation of prostate cancer cells in-vitro. The methodology involved treating androgen sensitive LnCap cells and androgen independent Du-145 with the novel PKC-ι inhibitor [1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy) methyl]cyclopentyl]-[1R-(1α, 2β, 3 β, 4 α)] (ICA-1) that targets a unique sequence (amino acid residues 469–475) in the catalytic domain of PKC-ι. Cell viability and number was quantified 24–72 hours following addition of either vehicle control or ICA-1 by Trypan blue exclusion. Additional ICA-1 was not added to the cells following the initial treatment. Results showed that at 24 hours post treatment, ICA-1 decreased the proliferation of LnCap cells by 46% (10 μM) and 83% (20 μM). ICA-1 reduced the proliferation of Du-145 cells at 24 hours by 43% (10 μM) and 51% (20 μM). The overexpression of PKC-ι in prostate cancer and the anti-proliferative effects of ICA-1 may translate into using PKC-i detection as a biomarker to identify patients that may benefit from anti-PKC-ι therapy with ICA-1 for personalized medicine. 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-437. doi:10.1158/1538-7445.AM2011-LB-437
Neonatal Sepsis and Other Infections Due to Group B Beta-Hemolytic Streptococci
Authors: Theodore C. Eickhoff, Jerome O. Klein, A. Kathleen Daly, David Ingall, Maxwell Finland
Journal: New England Journal of Medicine (1964)

BETA-hemolytic streptococci of Lancefield Group B have been implicated in human disease almost from the time when the precipitin-grouping technic first came into use.1 2 3 Since that time additional reports4 5 6 7 8 have established the fact that these organisms occasionally cause severe infection in parturient women, and less frequently in other adult patients and in newborn infants. Streptococcus agalactiae, the species designation9 of Group B streptococcus, has been recognized for many years at the Boston City Hospital from its characteristic colonial morphology on suitable solid mediums10 and observed frequently in primary cultures from obstetric patients and newborn infants. Recently, there appeared to be . . .
Abstract 4993: Nicotine induced EMT and metastasis of human NSCLC : Role of beta-arrestin-1
Authors: Smitha Pillai, Jose Trevino, Bhupendra Rawal, Sandeep Singh, Xueli Li, Michael Schell, Eric Haura, Gerold Bepler, Srikumar Chellappan
Journal: Cancer Research (2011)

Abstract Cigarette smoking is a major risk factor in the development of non-small cell lung cancer (NSCLC), which accounts for 80% of all lung cancers. Nicotine, an active component of tobacco smoke has been found to induce proliferation, invasion and epithelial-mesenchymal transition in NSCLC cell lines and promote the metastasis of NSCLC in mice. Nicotine induces cell proliferation utilizing a scaffolding protein, β-arrestin-1, which translocates to nucleus and associates with E2F1 transcription factor in response to nicotine stimulation. Here we demonstrate that mesenchymal markers such as vimentin and fibronectin are E2F1 regulated and β-arrestin-1 is involved in regulating nicotine induced expression of these genes. Vimentin and fibronectin promoters were E2F responsive and E2F1 could be detected on these promoters by chromatin immunoprecipitation (ChIP) assays. Depletion of β-arrestin-1 resulted in down-regulation of vimentin and fibronectin expression as well as inhibition of nicotine induced invasion of cells. Quantitative RT-PCR conducted on patient samples revealed a significant correlation between the levels of β-arrestin-1 and the expression of these genes. A microarray analysis conducted on nicotine stimulated parental A549 cells and those lacking β-arrestin-1 showed that about 290 genes were upregulated in the absence of β-arrestin-1, while 787 genes were downregulated. These included genes for transcription factors, growth factor receptors and signaling molecules. We further analyzed the global association of β-arrestin-1 in the genomic region upon nicotine stimulation by ChIP-sequencing and found that β-arrestin-1 is recruited on the promoters of many genes that regulate EMT such as ZEB2 (Zinc Finger E-box Binding Homeobox-2) as well as other regulatory pathways. ChIP assays conducted on NSCLC cell lines revealed the association of β-arrestin-1 on ZEB1 (Zinc Finger E-box Binding Homeobox-1) and ZEB2 promoters. Depletion of β-arrestin-1 in A549 cells resulted in the downregulation of ZEB1 and ZEB2. Additionally, in an orthotopic lung cancer model in SCID-beige mice, implantation of A549-luciferase stable cells lacking β-arrestin-1 showed a decrease in primary tumor growth and also resulted in significantly lower levels of nicotine-induced metastasis when compared to controls. Taken together, these data suggest that β-arrestin-1 contributes to nicotine induced progression and metastasis of NSCLC, especially in patients exposed to tobacco smoke. Further, β-arrestin-1 and its associated molecules might be targeted for the development of novel agents to combat NSCLC. 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 4993. doi:10.1158/1538-7445.AM2011-4993
P1019 VALIDATION AND COMPARISON OF NON-INVASIVE MARKERS OF LIVER FIBROSIS IN WEST-AFRICAN PATIENTS WITH CHRONIC HEPATITIS B LIVING IN THE GAMBIA
Authors: M. Lemoine, Y. Shimakawa, R. Goldin, M. Khalil, J. Lloyd, P. Suso, S. Nayagam, H. Freeya Njai, M. Taal, G. Ndow, U. D'Alessandro, R. Njie, M. Thursz
Journal: Journal of Hepatology (2014)
Myocardial Metastases From Renal Cell Carcinoma Mimicking Ischemia on Myocardial Perfusion Scintigraphy
Authors: Matthieu Pelletier-Galarneau, Rebecca Hibbert, Lionel S. Zuckier
Journal: Clinical Nuclear Medicine (2014)

A 60-year-old man with history of metastatic renal cell carcinoma and atypical chest pain was referred for dipyridamole 99mTc-tetrofosmin perfusion scintigraphy (MPS). Two years earlier, the patient was noted to have myocardial metastases on cardiac MRI. On the MPS, perfusion defects were present at stress in multiple vascular territories; resting myocardial uptake was homogeneous. These findings suggested multivessel atherosclerotic heart disease. In fact, retrospective rigid fusion with prior chest CT and cardiac MRI demonstrated that the reversible perfusion defects corresponded to metastatic deposits in the myocardium. This unusual case illustrates how myocardial metastases can mimic ischemia on MPS.
Cerebral Disorders after Open-Heart Operations
Authors: Sid Gilman
Journal: New England Journal of Medicine (1965)

ALTHOUGH development of the extracorporeal pump oxygenator has permitted rapid advances in cardiac surgery it has exposed the central nervous system to injury from a variety of agents despite the use of hypothermia to decrease its metabolic demands. The hazard of arterial air embolism has been reduced by refinement of oxygenators,1 2 3 4 but air emboli remain a threat, usually from trapping of air in the left ventricle at the termination of the operative procedure, despite careful evacuation and replacement with absorbable gases.5,6 Improperly designed coronary-suction devices may also be a source of air embolism.7 Embolization of silicone material from antifoam . . .
PI3K/AKT Activation and Response in Phase IB: AKT Inhibitor GDC-0068 with Docetaxel (D) Or MFOLFOX6 (F) in Refractory Solid Tumors
Authors: R. Meng, L.R. Molife, L. de Mattos-Arruda, A. Hollebecque, S.J. Isakoff, D. Roda, Y. Yan, A. Cervantes, J.C. Soria, J. Mateo, G. Argiles, J.C. Bendell
Journal: Annals of Oncology (2013)
Abstract P5-05-12: Heparan Sulfatase 2 Regulates Breast Cancer Tumorigenesis and Promotes Invasive Ductal Lesions
Authors: A Khurana, H McKean, J Mcguire, L Roberts, MP Goetz, V. Shridhar
Journal: Cancer Research (2010)

Abstract Ductal carcinoma in situ (DCIS) of the breast is a heterogenous group of proliferative cellular lesions that have the potential to become invasive. Very little is known about the molecular alterations involved in the progression from DCIS to invasive ductal carcinoma (IDC). Heparan endosulfatases HSulf-1 and -2 catalyze or edit sulfate moieties on heparan sulfate proteoglycans and have been implicated in modulating heparin binding growth factor signaling. Several studies have suggested that while expression of HSulf-1 is down-regulated and is considered a tumor suppressor gene, expression of HSulf-2 is over-expressed in primary breast tumors and cell lines. However, the role of HSulf-2 in breast tumorigenesis is poorly understood. Here we have evaluated the effect of HSulf-2 in an in vivo model of breast cancer progression (MCF10DCIS.com). These cells form comedo type DCIS and progress to IDC when transplanted in immune-deficient mice and therefore are an ideal model to study breast cancer progression. Methods: Stable clones depleted of HSulf-2 in MCF10DCIS.com cells were generated and injected into mouse mammary fat pads with non-targeted control shRNA clones (NTC) as controls. HSulf-1, HSulf-2, smooth muscle actin immunostaining and H&amp;E staining was perfromed at weeks 3, 5 and 7. Matrixmetallo Protease (MMP) expression by real time PCR was evaluated at Weeks 3 and 5 in both groups. Results: A significant reduction in tumor growth was observed in HSulf-2 depleted clones compared to NTC clones (p=&amp;lt;0.01). HSulf-2 immunohistochemical staining showed distinct pattern of staining localized to ductal lesions as well as stromal (myoepithelial and myofibroblasts cells). In contrast, the closely related family member, HSulf-1 expression was restricted largely to stromal and myoepithelial layer in ductal lesions. While HSulf-2 staining remained intense from weeks 3 to 7, HSulf-1 expression was diminished during the same time period. In NTC clones, ductal like lesions were observed by week 3 with disruption of the basement membrane and appearance of invasive phenotype by weeks 5 and 7. In contrast, HSulf2 knockdown xenografts showed retention of ductal like structures even at week 5 and retention of basement membrane (p=&amp;lt;0.05). Additionally marked necrotic areas were also observed in HSulf-2 silenced clones. Previous studies have shown that the malignant epithelium induces the development of the stroma necessary for the development of invasive phenotype. Consistent with this observation, we demonstrated decreased MMP expression in xenografts derived from HSulf-2 depleted clones compared with NTC xenografts (p=&amp;lt;0.05). Conclusions: Our data suggest that HSulf-2 may play an important role in the transition from DCIS to an invasive phenotype (IDC) potentially by up regulating MMP expression and activity. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-12.
Site and Nature of Airway Obstruction in Chronic Obstructive Lung Disease
Authors: James C. Hogg, Peter T. Macklem, W. M. Thurlbeck
Journal: New England Journal of Medicine (1968)

We have wedged a small catheter in airways 2 to 3 mm in diameter in excised human lungs to have measure airway resistance central (Rc) and peripheral (Rp) to this site. In five normal lungs, R accounted for only 25 per cent total airway resistance (RL) and averaged 0.18 cm of water per liter per second. In seven patients with emphysema Rp was increased from four to 40 times. Rp was also increased in one case of bronchiectasis and another of bronchiolitis. In all, Rc scattered around the normal value. Bronchographic and histologic studies showed that Rp was increased because of mucus plugging, narrowing and obliteration of the small airways. Disease of small airways may be common to various chronic obstructive lung diseases. Because Rp is normally so small, there may be considerable obstruction in peripheral airways that would affect ventilation distribution and gas exchange but would have little effect on function tests designed to reveal obstruction. When total airway resistance is elevated to a clinically detectable level by disease in the small airways, obstruction is much more severe than is generally recognized.