tbuckley/cabot-search huggingface dataset:
Novel Blood-Based, Five-Gene Biomarker Set for the Detection of Colorectal Cancer
Authors: Mark Han, Choong Tsek Liew, Hong Wei Zhang, Samuel Chao, Run Zheng, Kok Thye Yip, Zhen-Ya Song, Hiu Ming Li, Xiao Ping Geng, Li Xin Zhu, Jian-Jiang Lin, K. Wayne Marshall, Choong Chin Liew
Journal: Clinical Cancer Research (2008)

We applied a unique method to identify genes expressed in whole blood that can serve as biomarkers to detect colorectal cancer (CRC).Total RNA was isolated from 211 blood samples (110 non-CRC, 101 CRC). Microarray and quantitative real-time PCR were used for biomarker screening and validation, respectively.From a set of 31 RNA samples (16 CRC, 15 controls), we selected 37 genes from analyzed microarray data that differed significantly between CRC samples and controls (P < 0.05). We tested these genes with a second set of 115 samples (58 CRC, 57 controls) using quantitative real-time PCR, validating 17 genes as differentially expressed. Five of these genes were selected for logistic regression analysis, of which two were the most up-regulated (CDA and MGC20553) and three were the most down-regulated (BANK1, BCNP1, and MS4A1) in CRC patients. Logit (P) of the five-gene panel had an area under the curve of 0.88 (95% confidence interval, 0.81-0.94). At a cutoff of logit (P) >+0.5 as disease (high risk), <-0.5 as control (low risk), and in between as an intermediate zone, the five-gene biomarker combination yielded a sensitivity of 94% (47 of 50) and a specificity of 77% (33 of 43). The intermediate zone contained 22 samples. We validated the predictive power of these five genes with a novel third set of 92 samples, correctly identifying 88% (30 of 34) of CRC samples and 64% (27 of 42) of non-CRC samples. The intermediate zone contained 16 samples.Our results indicate that the five-gene biomarker panel can be used as a novel blood-based test for CRC.
Histologic Results of Para-Aortic Lymphadenectomy in Patients Treated for Stage IB2/II Cervical Cancer With Negative [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Scans in the Para-Aortic Area
Authors: Mathias Boughanim, Sophie Leboulleux, Annie Rey, Chi Tuan Pham, Yaelle Zafrani, Pierre Duvillard, Jean Lumbroso, Christine Haie-Meder, Martin Schlumberger, Philippe Morice
Journal: Journal of Clinical Oncology (2008)

Histologic results of complete para-aortic lymphadenectomy were studied in patients treated for stage IB2/II cervical carcinoma who had no para-aortic uptake on [(18)F]fluorodeoxyglucose positron emission tomography combined with integrated computed tomography (FDG-PET/CT).Patients were treated between 2004 and 2006 for stage IB2/II cervical cancer. Magnetic resonance imaging of the abdomen and pelvis and FDG-PET/CT were initially performed. Patients with no para-aortic abnormalities were treated with external pelvic radiation therapy and concomitant chemotherapy followed by utero-vaginal brachytherapy. Para-aortic lymphadenectomy was then performed. FDG-PET/CT images were reviewed by two nuclear medicine specialists.Thirty-eight patients were studied. Three patients had histologically proven para-aortic involvement (metastatic nodes with capsular rupture in the para-aortic area), leading to a negative predictive value of 92% for para-aortic nodal involvement.In this study, three of 38 patients with no para-aortic uptake on [(18)F]FDG-PET/CT imaging had histologically proven para-aortic node involvement. PET/CT imaging without histologic examination of the para-aortic area used to determine radiation therapy fields in stage IB2/II cervical cancer would overlook 8% of patients with histologic para-aortic nodal involvement.
Effects of well-defined ischemia on myocardial lysosomal and microsomal enzymes in a canine model.
Authors: F F Kennett, W B Weglicki
Journal: Circulation Research (1978)

We have used a new technique for extraction of myocardial membranes (0.25 M sucrose, 0.6 M KCl) to isolate particulate and soluble proteins and enzymatic activities in an effort to quantify changes characteristic of progressive ischemia. Myocardial blood flow (MBF) was measured with microspheres (15 micrometer diameter) in all samples of tissue used for assay of proteins and enzymatic activities; MBF to the moderately ischemic areas (M-ischemia) was 53% of control (H-control); MBF to the severely ischemic areas (L-ischemia) was 9% of control. Significant decreases (P less than 0.001) in content of protein were seen in all post 1,000 g pellets and supernatant fluids in the L-ischemia zones; particulate lysosomal enzymatic activity was significantly decreased (P less than 0.001) in all four post 1,000 g pellets (2,500 g to 140,000 g) of the L-ischemic areas (for N-acetyl-beta-glucosaminidase and beta-glucuronidase). The increase in percent free activity of lysosomal enzymes (index of loss of latency) also was highly significant (P less than 0.001) in all particulate fractions of the L-ischemic areas. In addition, about 45% of the total activity of the microsomal marker enzyme, rotenone-insensitive NADH cytochrome C reductase (RINCR), was found in the 140,000 g pellet of H-control tissue (9.9 micronmol/min per g); this activity fell to 8.1 micronmol/min per g in M-ischemic areas (P less than 0.001) and to 5.3 micronmol/min per g in L-ischemic areas (P less than 0.001). This study demonstrates that changes in myocardial proteins, lysosomes, and other membrane-bound enzymes (RINCR) may provide reproducible bichemical parameters for assessing ischemic myocardial injury.
Loss of the Tumor Suppressor PML in Human Cancers of Multiple Histologic Origins
Authors: C. Gurrieri, P. Capodieci, R. Bernardi, P. P. Scaglioni, K. Nafa, L. J. Rush, D. A. Verbel, C. Cordon-Cardo, P. P. Pandolfi
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The PML gene is fused to the RARα gene in the vast majority of acute promyelocytic leukemias (APL) and has been implicated in the control of key tumor-suppressive pathways. However, its role in the pathogenesis of human cancers other than APL is still unclear. We therefore assessed the status and expression of the PML gene in solid tumors of multiple histologic origins. Methods: We created tumor tissue microarrays (TTMs) with samples from patients with colon adenocarcinoma (n = 109), lung carcinoma (n = 19), prostate adenocarcinoma (n = 36), breast carcinoma (n = 38), central nervous system (CNS) tumors (n = 51), germ cell tumors (n = 60), thyroid carcinoma (n = 32), adrenal cortical carcinoma (n = 12), and non-Hodgkin's lymphoma (n = 251) and from normal tissue corresponding to each histotype and analyzed PML protein and mRNA expression by immunohistochemistry and in situ hybridization, respectively. Tumor cell lines (n = 64) of various histologic origins were analyzed for PML protein and mRNA expression by immunofluorescence and northern blotting, respectively. DNA from microdissected tumor samples and cell lines was analyzed for PML mutations and loss of heterozygosity (LOH). For some tumor types, the association between PML expression and tumor stage and grade was analyzed. Statistical tests were two-sided. Results: All normal tissues expressed PML protein. PML protein expression was reduced or abolished in prostate adenocarcinomas (63% [95% confidence interval {CI} = 48% to 78%] and 28% [95% CI = 13% to 43%], respectively), colon adenocarcinomas (31% [95% CI = 22% to 40%] and 17% [95% CI = 10% to 24%]), breast carcinomas (21% [95% CI = 8% to 34%] and 31% [95% CI = 16% to 46%]), lung carcinomas (36% [95% CI = 15% to 57%] and 21% [95% = 3% to 39%]), lymphomas (14% [95% CI = 10% to 18%] and 69% [95% CI = 63% to 75%]), CNS tumors (24% [95% CI = 13% to 35%] and 49% [95% CI = 36% to 62%]), and germ cell tumors (36% [95% CI = 24% to 48%] and 48% [95% CI = 36% to 60%]) but not in thyroid or adrenal carcinomas. Loss of PML protein expression was associated with tumor progression in prostate cancer (the progression from prostatic intraepithelial neoplasia to invasive carcinoma was associated with complete PML loss; P<.001), breast cancer (complete PML loss was associated with lymph node metastasis; P = .01), and CNS tumors (complete PML loss was associated with high-grade tumors ; P = .003). PML mRNA was expressed in all tumor and cell line samples. The PML gene was rarely mutated and was not subject to LOH. Conclusions: PML protein expression is frequently lost in human cancers of various histologic origins, and its loss associates with tumor grade and progression in some tumor histotypes.
CEREBELLUM-DEPENDENT LEARNING: The Role of Multiple Plasticity Mechanisms
Authors: Edward S. Boyden, Akira Katoh, Jennifer L. Raymond
Journal: Annual Review of Neuroscience (2004)

The cerebellum is an evolutionarily conserved structure critical for motor learning in vertebrates. The model that has influenced much of the work in the field for the past 30 years suggests that motor learning is mediated by a single plasticity mechanism in the cerebellum: long-term depression (LTD) of parallel fiber synapses onto Purkinje cells. However, recent studies of simple behaviors such as the vestibulo-ocular reflex (VOR) indicate that multiple plasticity mechanisms contribute to cerebellum-dependent learning. Multiple plasticity mechanisms may provide the flexibility required to store memories over different timescales, regulate the dynamics of movement, and allow bidirectional changes in movement amplitude. These plasticity mechanisms must act in combination with appropriate information-coding strategies to equip motor-learning systems with the ability to express learning in correct contexts. Studies of the patterns of generalization of motor learning in the VOR provide insight about the coding of information in neurons at sites of plasticity. These principles emerging from studies of the VOR are consistent with results concerning more complex behaviors and thus may reflect general principles of cerebellar function.
The Significance of G Protein-Coupled Receptor Crystallography for Drug Discovery
Authors: John A. Salon, David T. Lodowski, Krzysztof Palczewski
Journal: Pharmacological Reviews (2011)

Crucial as molecular sensors for many vital physiological processes, seven-transmembrane domain G protein-coupled receptors (GPCRs) comprise the largest family of proteins targeted by drug discovery. Together with structures of the prototypical GPCR rhodopsin, solved structures of other liganded GPCRs promise to provide insights into the structural basis of the superfamily9s biochemical functions and assist in the development of new therapeutic modalities and drugs. One of the greatest technical and theoretical challenges to elucidating and exploiting structure-function relationships in these systems is the emerging concept of GPCR conformational flexibility and its cause-effect relationship for receptor-receptor and receptor-effector interactions. Such conformational changes can be subtle and triggered by relatively small binding energy effects, leading to full or partial efficacy in the activation or inactivation of the receptor system at large. Pharmacological dogma generally dictates that these changes manifest themselves through kinetic modulation of the receptor9s G protein partners. Atomic resolution information derived from increasingly available receptor structures provides an entrée to the understanding of these events and practically applying it to drug design. Supported by structure-activity relationship information arising from empirical screening, a unified structural model of GPCR activation/inactivation promises to both accelerate drug discovery in this field and improve our fundamental understanding of structure-based drug design in general. This review discusses fundamental problems that persist in drug design and GPCR structural determination.
Can Women With Early-Stage Breast Cancer Make an Informed Decision for Mastectomy?
Authors: E. Dale Collins, Caroline P. Moore, Kate F. Clay, Stephen A. Kearing, Annette M. O'Connor, Hilary A. Llewellyn-Thomas, Richard J. Barth, Karen R. Sepucha
Journal: Journal of Clinical Oncology (2008)

The purpose of this study was to measure the degree to which informed women chose mastectomy, and to reveal their reasons for this choice.This was a prospective cohort study of patients radiographically and pathologically eligible for either mastectomy or breast-conserving surgery (BCS; n = 125). Participants completed questionnaires at three time points: baseline, after viewing a decision aid, and after a surgical consultation. Questionnaires assessed clinical history, preference for participation in decision making, information comprehension, values, decisional conflict, and preferred treatment.Of 125 participants, 44 (35%) chose mastectomy. Most understood that BCS and mastectomy offer an equivalent survival benefit (98%) and that BCS has a slightly higher local recurrence risk (63%); most accurately identified the magnitude of ipsilateral local recurrence risk (91%). Values assigned to three treatment attributes/outcomes ("remove breast for peace of mind," "avoid radiation," and "keep breast") clearly discriminated between patients choosing mastectomy or BCS. High decisional conflict scores improved after both the decision aid and surgical consultation.Although conventional wisdom may view BCS as the preferred treatment, a notable proportion of well informed women choose mastectomy. Whereas prior studies have linked objective factors to treatment choice, this study reveals subjective preferences that underlie decision making. The systematic use of a decision aid before the surgical consultation may help women make informed, values-based decisions, while clearly reducing decisional conflict.
Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance
Authors: Morten B. Sorensen, Peter Collins, Paul J.L. Ong, Carolyn M. Webb, Christopher S. Hayward, Elizabeth A. Asbury, Peter D. Gatehouse, Andrew G. Elkington, Guang Z. Yang, Ali Kubba, Dudley J. Pennell
Journal: Circulation (2002)

Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women.Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (>1 year use; mean age 29+/-4 years) and in 10 controls (mean age 30+/-4 years, P=0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (n=12) in DMPA users and during menstruation and midcycle (n=9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively P<0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, P<0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, P=0.23). Estradiol levels were significantly correlated to FMD (r=0.43, P<0.01).Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.
Limitations in the Use of Indices Using Glucose and Insulin Levels to Predict Insulin Sensitivity
Authors: Veeradej Pisprasert, Katherine H. Ingram, Maria F. Lopez-Davila, A. Julian Munoz, W. Timothy Garvey
Journal: Diabetes Care (2012)

OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SIisOGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SIisOGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381–0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SIisOGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SIisOGTT are reliable in studies that include AA males.
Vascular Targeting and Antiangiogenesis Agents Induce Drug Resistance Effector GRP78 within the Tumor Microenvironment
Authors: Dezheng Dong, Bryce Ko, Peter Baumeister, Steven Swenson, Fritz Costa, Frank Markland, Caryn Stiles, John B. Patterson, Susan E. Bates, Amy S. Lee
Journal: Cancer Research (2005)

Abstract Therapeutic targeting of the tumor vasculature that destroys preexisting blood vessels of the tumor and antiangiogenesis therapy capitalize on the requirement of tumor cells on an intact vascular supply for oxygen and nutrients for growth, expansion and metastasis to the distal organs. Whereas these classes of agents show promise in delaying tumor progression, they also create glucose and oxygen deprivation conditions within the tumor that could trigger unintended prosurvival responses. The glucose-regulated protein GRP78, a major endoplasmic reticulum chaperone, is inducible by severe glucose depletion, anoxia, and acidosis. Here we report that in a xenograft model of human breast cancer, treatment with the vascular targeting agent, combretastatin A4P, or the antiangiogenic agent, contortrostatin, promotes transcriptional activation of the Grp78 promoter and elevation of GRP78 protein in surviving tumor cells. We further show that GRP78 is overexpressed in a panel of human breast cancer cells that has developed resistance to a variety of drug treatment regimens. Suppression of GRP78 through the use of lentiviral vector expressing small interfering RNA sensitizes human breast cancer cells to etoposide-mediated cell death. Our studies imply that antivascular and antiangiogenesis therapy that results in severe glucose and oxygen deprivation will induce GRP78 expression that could lead to drug resistance.
A bronchoscopic brush biopsy study of large airway mucosal pathology in smokers with chronic bronchitis and in healthy nonsmokers
Authors: GC Riise, S Larsson, BA Andersson
Journal: European Respiratory Journal (1992)

We investigated the use of bronchial brush biopsies of the bronchial epithelium as a diagnostic tool in common airway diseases. Flexible fibreoptic bronchoscopy was performed on 22 smokers with nonobstructive chronic bronchitis and on 14 healthy nonsmoking individuals. Ten of the smokers had recurrent infectious exacerbations. Cell samples were taken from carinal and subsegmental levels of the bronchial tree with a standard cytological brush, and a differential count was made of the different cell types. Smokers with chronic bronchitis had significantly more goblet cells (mean 20.0, SD 8.6), and less ciliated epithelial cells (mean 74.1, SD 9.4), than the healthy nonsmokers (mean 9.2, SD 3.9 and mean 84.7, SD 6.6, respectively). No such changes were found between the chronic bronchitis groups with or without infectious exacerbations. Thus, bronchial brush biopsies can be used as a complement to standard bronchial biopsies in the investigation of airway diseases other than pulmonary malignancies.
Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer
Authors: N. Xenidis, I. Vlachonikolis, D. Mavroudis, M. Perraki, A. Stathopoulou, N. Malamos, C. Kouroussis, S. Kakolyris, S. Apostolaki, N. Vardakis, E. Lianidou, V. Georgoulias
Journal: Annals of Oncology (2003)
Cholera — A Possible Endemic Focus in the United States
Authors: Paul A. Blake, Donald T. Allegra, John D. Snyder, Timothy J. Barrett, Louise McFarland, Charles T. Caraway, John C. Feeley, John P. Craig, John V. Lee, Nancy D. Puhr, Roger A. Feldman
Journal: New England Journal of Medicine (1980)

In September and October 1978, after a case of cholera had been discovered in southwestern Louisiana, 10 more Vibrio cholerae O-Group 1 infections were detected in four additional clusters. All 11 infected persons had recently eaten cooked crabs from five widely separated sites in the coastal marsh, and a matched-triplet case-control study showed a significant relation between cholera and eating such crabs (P = 0.007). V. cholerae O1 was isolated from estuarine water, from fresh shrimp, from a leftover cooked crab from a patient's refrigerator, and from sewage in six towns, including three without identified cases. All isolates in Louisiana and an isolate from a single unexplained case in Texas in 1973 were biotype El Tor and serotype inaba; they were hemolytic and of a phage type unique to the United States--suggesting that the organism persisted undetected along the Gulf Coast for at least five years.