tbuckley/cabot-search huggingface dataset:
Human Epidermal Growth Factor Receptor 2 Testing in Primary Breast Cancer in the Era of Standardized Testing: A Canadian Prospective Study
Authors: Wedad M. Hanna, Penny J. Barnes, Martin C. Chang, C. Blake Gilks, Anthony M. Magliocco, Henrike Rees, Louise Quenneville, Susan J. Robertson, Sandip K. SenGupta, Sharon Nofech-Mozes
Journal: Journal of Clinical Oncology (2014)

Therapies that target overexpression of human epidermal growth factor receptor 2 (HER2) rely on accurate and timely assessment of all patients with new diagnoses. This study examines HER2 testing of primary breast cancer tissue when performed with immunohistochemistry (IHC) and additional in situ hybridization (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false-negative HER2 tests, defined as IHC 0/1+ with an ISH ratio ≥ 2.0, in eight pathology centers across Canada.Whole sections of surgical resections or tissue microarrays (TMAs) from invasive breast carcinoma tissue were tested by both IHC and ISH using standardized local methods. Samples were scored by the local breast pathologist, and consecutive HER2-negative IHC results (IHC 0/1+) were compared with the corresponding fluorescence or silver ISH result.Overall, 711 surgical excisions of primary breast cancer were analyzed by IHC and ISH; HER2 and chromosome 17 centromere (CEP17) counts were available in all cases. The overall rate of false-negative samples was 0.84% (six of 711 samples). Interpretable IHC and ISH scores were available in 1,212 cases from TMAs, and the overall rate of false-negative cases was 1.6% (16 of 978 cases).Our observation confirms that IHC is an adequate test to predict negative HER2 status in primary breast cancer in surgical excision specimens, even when different antibodies and IHC platforms are used. The study supports the American Society of Clinical Oncology/College of American Pathologists and Canadian testing algorithms of using IHC followed by ISH for equivocal cases.
Phase II Evaluation of Nanoparticle Albumin–Bound Paclitaxel in Platinum-Sensitive Patients With Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer
Authors: Michael G. Teneriello, Paul C. Tseng, Mark Crozier, Carlos Encarnacion, Kenneth Hancock, Mark J. Messing, Kristi A. Boehm, Alicia Williams, Lina Asmar
Journal: Journal of Clinical Oncology (2009)

Patients with recurrent ovarian, peritoneal, or fallopian tube cancer have limited therapeutic options. There are no reports of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with recurrent platinum-sensitive disease. We report efficacy and toxicity with nab-paclitaxel in this group.Forty-seven patients enrolled (44 assessable patients). Main inclusion criteria were histologically or cytologically confirmed epithelial cancer of the ovary, fallopian tube, or peritoneum (any stage, grade 2 to 3 if stage I) and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or elevated CA-125 (> 70 U/mL) in patients without measurable disease. Patients received nab-paclitaxel 260 mg/m(2) administered intravenously for 30 minutes on day 1 of a 21-day cycle for six cycles or until disease progression.Median age was 65.5 years; 76% of patients had stage IIIC or IV disease, 81% had Eastern Cooperative Oncology Group performance status of 0, and 94% had prior surgery. For assessable patients, the objective response rate (ORR) was 64% (15 complete responses [CR] and 13 partial responses [PR] among 44 assessable patients). In patients evaluated with RECIST only, the ORR was 45% (one CR and four PR of 11 patients). In patients with only elevated CA-125, ORR was 82% (seven CRs and two PRs of 11 patients). In patients meeting both RECIST and CA-125 criteria, the ORR was 64% (seven CRs and seven PRs of 22 patients). Median time to response was 1.3 months (range, 0.5 to 4.8 months). Estimated median progression-free survival was 8.5 months. The most frequent grade 3 to 4 treatment-related toxicities were neutropenia (24%) and neuropathy (9%).Nab-paclitaxel is active in this group of patients with recurrent ovarian, peritoneal, or fallopian tube cancer. The ORR was 64%. Toxicities were manageable. Further studies of nab-paclitaxel in combination with platinum are warranted.
Genetic Activation of the <i>MET</i> Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric Cancer
Authors: Francesco Graziano, Nadia Galluccio, Paola Lorenzini, Annamaria Ruzzo, Emanuele Canestrari, Silvia D'Emidio, Vincenzo Catalano, Valerio Sisti, Claudia Ligorio, Francesca Andreoni, Eliana Rulli, Enrico Di Oto, Giammaria Fiorentini, Costantino Zingaretti, Michele De Nictolis, Federico Cappuzzo, Mauro Magnani
Journal: Journal of Clinical Oncology (2011)

Purpose To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. Patients and Methods A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (&lt; 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). Results In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P &lt; .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P &lt; .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. Conclusion In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.
DawnRank: discovering personalized driver genes in cancer
Authors: Jack P Hou, Jian Ma
Journal: Genome Medicine (2014)

Large-scale cancer genomic studies have revealed that the genetic heterogeneity of the same type of cancer is greater than previously thought. A key question in cancer genomics is the identification of driver genes. Although existing methods have identified many common drivers, it remains challenging to predict personalized drivers to assess rare and even patient-specific mutations. We developed a new algorithm called DawnRank to directly prioritize altered genes on a single patient level. Applications to TCGA datasets demonstrated the effectiveness of our method. We believe DawnRank complements existing driver identification methods and will help us discover personalized causal mutations that would otherwise be obscured by tumor heterogeneity. Source code can be accessed at http://bioen-compbio.bioen.illinois.edu/DawnRank/.
Oxidant Air Pollution and Athletic Performance
Authors: Walborg S. Wayne
Journal: JAMA (1967)

The effect of Los Angeles' oxidizing type of air pollution on athletic performance was studied in 21 competitive meets of high school cross-country track runners from 1959 to 1964. Since running times tend to improve throughout the season, team performance at a meet was evaluated by determining the percent of boys who failed to improve when their running time was compared to that run at the previous meet on the same course. The highest correlation to team performance is that of the oxidant level in the hour before the race. Neither carbon monoxide, temperature, nor humidity shows any relationship to performance. The specificity of the effect to a biologically meaningful time and the very high correlation are convincing evidence of a cause and effect relationship. The mechanism by which oxidants affect performance may be directly physiological or may be decreased motivation due to discomfort.
Concerns About Using the Patient Safety Indicator-90 Composite in Pay-for-Performance Programs
Authors: Ravi Rajaram, Cynthia Barnard, Karl Y. Bilimoria
Journal: JAMA (2015)

This Viewpoint discusses how the Center for Medicare and Medicaid’s use of Patient Safety Indicator-90 in pay-for-performance programs falls short in its attempt to accurately and fairly measure patient harm.
Cold water immersion (cryotherapy) for preventing muscle soreness after exercise
Authors: Joanna Diong, Steven J Kamper
Journal: British Journal of Sports Medicine (2013)

▸  Bleakley C , McDonough S, et al. Cold-water immersion (cryotherapy) for preventing and treating muscle soreness after exercise. Cochrane Database Syst Rev 2012; 2 :CD008262.

Intense exercise involving eccentric muscle contractions often leads to delayed onset muscle soreness. Eccentric muscle contractions cause damage to muscle fibres which lead to pain, stiffness and loss in joint range of motion.1 The anti-inflammatory effects of cold water immersion, a form of cryotherapy where the limb(s) or body is submerged in a cold water bath, are thought to reduce pain and swelling following acute soft tissue injury.2 Cold water immersion immediately after exercise may have anti-inflammatory effects and prevent delayed onset muscle soreness, however these effects remain unclear.

This study aimed to determine the effects of cold water immersion on the prevention of muscle soreness after exercise.

The following databases were searched up to 2010 or 2011: the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL, Medline, EMBASE, CINAHL, PEDro and British Nursing Index and archive. The authors also searched databases for ongoing trials and hand-searched journals and conference proceedings. Experts in the field were contacted for relevant data from published, unpublished or ongoing studies.

Randomised and quasi-randomised trials examining cold water immersion for preventing muscle soreness after exercise were included. Participants had to receive cold …
Biochemical Studies on Mitochondria Isolated From Normal and Neoplastic Tissues of the Mouse Mammary Gland 2
Authors: Michael T. White, S. Nandi
Journal: JNCI Journal of the National Cancer Institute (1976)

Mitochondria isolated from spontaneous and transplanted mammary adenocarcinomas of two strains of mice were compared, by various biochemical criteria, to mitochondria from mammary glands of midpregnant or hormonally stimulated, cancer-free mice. The specific activities of several mitochondrial enzymes including cytochrome oxidase, alpha-glycerophosphate oxidase, and succinate dehydrogenase were twofold to threefold lower, whereas the activity of monoamine oxidase was two fold higher in tumor mitochondria. Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria. In addition, mitochondrial polypeptide composition was analyzed by electrophoresis on sodium dodecyl sulfate-urea polyacrylamide gels. Midpregnant mammary gland and mammary tumor mitochondria were similar in polypeptide composition; however, several differences were observed. A high-molecular-weight polypeptide, present in mid-pregnant mammary gland mitochondria was absent from tumor mitochondria. Also, tumor mitochondria contained an additional high-molecular-weight polypeptide not found in the midpregnant mammary gland. There were numerous differences in the relative proportions of many polypeptides common to both tumor and midpregnant mammary gland mitochondria.
The Role of Blood Pressure Variability in the Development of Nephropathy in Type 1 Diabetes
Authors: Eric S. Kilpatrick, Alan S. Rigby, Stephen L. Atkin
Journal: Diabetes Care (2010)

OBJECTIVE Increases in blood pressure and visit-to-visit variability have both been found to independently increase the likelihood of cardiovascular events in nondiabetic individuals. This study has investigated whether each may also influence the development of microvascular complications in type 1 diabetes by examining data from the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS Using binary longitudinal multiple logistic regression, mean systolic (SBP) and diastolic (DBP) blood pressure as well as annual visit-to-visit variability (SD.SBP and SD.DBP, respectively) was related to the risk of the development/progression of nephropathy and retinopathy in initially normotensive subjects who did not become pregnant during the DCCT. RESULTS Mean SBP and SD.SBP were independently predictive of albuminuria (odds ratio 1.005 [95% CI 1.002–1.008], P &amp;lt; 0.001 and 1.093 [1.069–1.117], P &amp;lt; 0.001, respectively, for 1 mmHg change), although SBP variability did not add to mean SBP in predicting retinopathy (0.999 [0.985–1.013], P = 0.93). DBP variability was also independently predictive of nephropathy (1.102 [1.068–1.137], P &amp;lt; 0.001) and not of retinopathy (0.991 [0.971–1.010], P = 0.37). Mean SBP was poorly related to SD.SBP (r2 &amp;lt; 0.01) as was mean DBP with SD. DBP (r2 &amp;lt; 0.01). CONCLUSIONS Visit-to-visit variability in blood pressure consistently independently added to mean blood pressure in predicting the risk of nephropathy, but not retinopathy, in the DCCT. This observation could have implications for the management and treatment of blood pressure in patients with type 1 diabetes.
Intentional Maps in Posterior Parietal Cortex
Authors: Richard A. Andersen, Christopher A. Buneo
Journal: Annual Review of Neuroscience (2002)

▪ Abstract The posterior parietal cortex (PPC), historically believed to be a sensory structure, is now viewed as an area important for sensory-motor integration. Among its functions is the forming of intentions, that is, high-level cognitive plans for movement. There is a map of intentions within the PPC, with different subregions dedicated to the planning of eye movements, reaching movements, and grasping movements. These areas appear to be specialized for the multisensory integration and coordinate transformations required to convert sensory input to motor output. In several subregions of the PPC, these operations are facilitated by the use of a common distributed space representation that is independent of both sensory input and motor output. Attention and learning effects are also evident in the PPC. However, these effects may be general to cortex and operate in the PPC in the context of sensory-motor transformations.
Markedly improved overall survival in 10 consecutive patients with metastatic basal cell carcinoma
Authors: C. Danial, B. Lingala, R. Balise, A.E. Oro, S. Reddy, A. Colevas, A.L.S. Chang
Journal: British Journal of Dermatology (2013)

Background Metastatic basal cell carcinoma (BCC) is a rare but life-threatening condition. Prior estimates of overall survival (OS) from time of diagnosis of distant metastasis to death are approximately 8–14 months. However, these estimates are based on analyses of case reports published prior to 1984. Objectives To assess an updated OS in patients with metastatic BCC at a single academic institution. Methods Using patients seen from 1997 to 2011, a retrospective chart review was performed on biopsy-confirmed cases of distant metastatic BCC at Stanford University School of Medicine. Kaplan–Meier analysis was used to determine OS and progression-free survival (PFS). Results Ten consecutive cases of distant metastatic BCC were identified. Median OS was 7·3 years [95% confidence interval (CI) 1·6–∞]; median PFS was 3·4 years (95% CI 1·1–5·2). Conclusions Our findings suggest that OS in patients with distant metastatic BCC may be more favourable than previously reported.
Identification of a Novel Nuclear Guanosine Triphosphate-Binding Protein Differentially Expressed in Renal Disease
Authors: NICHOLAS J. LAPING, BARBARA A. OLSON, YUAN ZHU
Journal: Journal of the American Society of Nephrology (2001)

Abstract. A novel guanosine triphosphate—binding protein, chronic renal failure gene (CRFG), was discovered by differential display PCR to be regulated differentially in renal disease. Within the rat kidney, CRFG mRNA was localized to the outer medulla and was highly expressed in epithelial cells. The specific renal expression of CRFG mRNA in the outer medulla was reduced dramatically in several rat models of renal disease, including diabetic nephropathy, partial nephrectomy, ischemia, and anti-Thy1.1—induced nephritis. CRFG was localized selectively in the nucleus of human and rodent cells, as determined by immunocytochemistry and green fluorescence fusion protein. Cellular mRNA levels of CRFG were also increased after serum administration, when cells proliferate. These data suggest that CRFG may be involved in regulating guanosine triphosphate—dependent nuclear events that are associated with cell proliferation and that are important in normal renal function and essential for growth and development.
Stat3/Socs3 Activation by IL-6 Transsignaling Promotes Progression of Pancreatic Intraepithelial Neoplasia and Development of Pancreatic Cancer
Authors: Marina Lesina, Magdalena U. Kurkowski, Katharina Ludes, Stefan Rose-John, Matthias Treiber, Günter Klöppel, Akihiko Yoshimura, Wolfgang Reindl, Bence Sipos, Shizuo Akira, Roland M. Schmid, Hana Algül
Journal: Cancer Cell (2011)
Tumor necrosis serum induces a serologically distinct population of NK cells.
Authors: M Chun, V Pasanen, U Hämmerling, G F Hämmerling, M K Hoffmann
Journal: The Journal of Experimental Medicine (1979)

Murine spleen cells generate nonspecific cytotoxic cells, referred to as natural killer (NK) cells, within 4 d of incubation in Mishell-Dutton cultures. This NK cell type does not arise in cultures of BALB/c.nu spleen cells or in cultures of T-cell depleted C57BL/6 spleen cells, indicating that its activation depends on T cells. Another type of NK cells is induced by tumor necrosis serum in murine spleen-cell cultures. It arises within 24 h and its activation does not depend on T cells. This cell type (and its precursor) expresses the recently discovered cell-surface marker Qa5 (controlled by the Q region of chromosome 17) that distinguishes this NK cell from the NK cell that depends for its activation on thymic function. Qa5+ NK cells are also induced by interferon.
Prognostic Significance of Tissue Factor in Pancreatic Ductal Adenocarcinoma
Authors: Nobuhiro Nitori, Yoshinori Ino, Yukihiro Nakanishi, Tesshi Yamada, Kazufumi Honda, Kazuyoshi Yanagihara, Tomoo Kosuge, Yae Kanai, Masaki Kitajima, Setsuo Hirohashi
Journal: Clinical Cancer Research (2005)

Abstract Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathologic significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of tumor cell immunopositivity, patients were divided into “negative TF” (0%), “weak TF” (&amp;lt;25%), or “high TF” (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary tumor (P = 0.0043), lymph node metastasis (P = 0.0043), lymphatic distant metastasis (P = 0.0039), advanced tumor-node-metastasis stage (P = 0.0002), and high tumor grade (P = 0.0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative tumors had a significantly better prognosis even if lymph node metastasis was present (P &amp;lt; 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.
Establishing the link between a specific pathology and atrial fibrillation
Authors: R Schuessler
Journal: Cardiovascular Research (2001)

See article by Shi et al. [5] (pages 217–225) in this issue. 

Atrial fibrillation (AF) is associated with numerous pathologies, as well as the normal aging process. The most common pathologies are valvular and ischemic heart disease, hyperthyroidism, hypertension, and cardiomyopathies. Less common etiologies, but still clearly associated with AF, include cardiac tumors, various inflammatory diseases, abnormal autonomic tone, and substance abuse [1]. What has become clear over the last 100 years of AF research is that at the electrophysiological level there are four interacting substrates that contribute to AF. These include: (1) premature impulse formation; (2) the magnitude and distribution of repolarization and refractory period; (3) the magnitude, distribution, and anisotropy of propagation velocity; and (4) the microscopic and macroscopic anatomy of the atria. The interaction of these factors determines … 

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Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate
Authors: Jonas Abrahamsson, Erik Forestier, Jesper Heldrup, Kirsi Jahnukainen, Ólafur G. Jónsson, Birgitte Lausen, Josefine Palle, Bernward Zeller, Henrik Hasle
Journal: Journal of Clinical Oncology (2010)

To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (≥ 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation.Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%).The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.
Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial
Authors: David P Dearnaley, Matthew R Sydes, John D Graham, Edwin G Aird, David Bottomley, Richard A Cowan, Robert A Huddart, Chakiath C Jose, John HL Matthews, Jeremy Millar, A Rollo Moore, Rachel C Morgan, J Martin Russell, Christopher D Scrase, Richard J Stephens, Isabel Syndikus, Mahesh KB Parmar
Journal: The Lancet Oncology (2007)