tbuckley/cabot-search huggingface dataset:
Influence of anthracycline- and taxane-based neoadjuvant chemotherapy on tumor HER2 protein expression in locally advanced breast cancers: results from the I-SPY TRIAL (CALGB 150007/150012 &amp; ACRIN 6657).
Authors: C Livasy, L Carey, A DeMichele, D Cowan, J Markey, D Little, I-SPY Clinical Investigators, L Dressler
Journal: Cancer Research (2009)

Abstract Abstract #703 Background: The I-SPY trial is a multi-institutional study of locally advanced breast cancers in which serial biopsies of breast tumors are performed at multiple timepoints, allowing comparison of tumor biomarker status before, during, and after therapy. Tumor HER2 status has an important role in predicting response to chemotherapy and targeted therapy in breast cancer. The aim of this study was to determine if the administration of neoadjuvant chemotherapy was associated with changes in tumor HER2 protein expression.&amp;#x2028; Methods: Eligible patients had biopsy-confirmed primary breast cancer measuring at least 3 cm. Required initial treatment was an anthracycline based neoadjuvant chemotherapy regimen: AC followed by T (91%), AC without T (6%), and chemotherapy beyond AC +/- T 2%. Serial core biopsies were performed at baseline (T1), after one cycle of AC (T2), intra-regimen (T3), and pre-surgery (T4). Immunohistochemistry (IHC) for HER2 was performed centrally on core samples at T1 and T2 and on post-surgery (PS) excision/mastectomy specimens (for patients with residual tumor). HER2 results were classified as negative, indeterminate, or overexpressed using conventional scoring criteria. Tumor HER2 status was compared between timepoints T1 and T2, T2 and PS, and T1 and PS. Patients receiving Herceptin therapy were excluded from this analysis. Additional molecular analysis is being performed and the IHC results will be compared with gene expression and phospho-HER2 results.&amp;#x2028; Results: 221 patients were enrolled and completed therapy. The median age was 49 years, with a range of 27-69. Median tumor size was 6 cm; 58% had clinically positive nodes. HER2 results were obtained centrally at baseline on 178 (80%) patients. 41 of 178 (23%) tumors were positive for HER2 overexpression. The overall pCR rate in HER2 positive patients was 52% compared to 19% for HER2 negative patients (p&amp;lt;0.001). Patient HER2 results were compared at T1 and T2 (n=154), T2 and PS (n=81), and T1 and PS (n=89). Nine of the 32 (28%) HER2 positive patients with multiple timepoint HER2 results were excluded due to receiving Herceptin therapy. The tumor HER2 status between timepoints is summarized in the table below.&amp;#x2028; &amp;#x2028; Conclusions: Tumor HER2 protein expression levels appear stable in patients undergoing neoadjuvant chemotherapy with anthracycline- and taxane-based regimens. Rare tumors (2-3%) showed a change from a HER2 positive result to a HER2 negative result during chemotherapy; these findings may be related to tumor heterogeneity rather than a true treatment-induced change in HER2 status.&amp;#x2028; Support: CALGB CA31964 and CA33601, ACRIN U01 CA079778 and CA080098, NCI SPORE CA58207. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 703.
A new deal for road crash victims
Authors: M. Haegi
Journal: BMJ (2002)

People do not generally expect to be affected by road traffic crashes—they are a horror that affects others. But that is not what the statistics say. For lifetime exposure, the average person in a developed country has a 1% risk of death and a 30% risk of injury.1

About 50% deaths occur at the site of the crash or during transport, and the rest of deaths occur in hospital.1 Many developed countries provide fast emergency help, which can be on the spot in five minutes in urban areas and in 20 minutes in rural areas. …
Gene Transfer Approaches for Gynecological Diseases
Authors: Mari Raki, Daniel T. Rein, Anna Kanerva, Akseli Hemminki
Journal: Molecular Therapy (2006)

Gene transfer presents a potentially useful approach for the treatment of diseases refractory to conventional therapies. Various preclinical and clinical strategies have been explored for treatment of gynecological diseases. Given the direst need for novel treatments, much of the work has been performed with gynecological cancers and ovarian cancer in particular. Although the safety of many approaches has been demonstrated in early phase clinical trials, efficacy has been mostly limited so far. Major challenges include improving gene transfer vectors for enhanced and selective delivery and achieving effective penetration and spread within advanced and complex tumor masses. This review will focus on current and developmental gene transfer applications for gynecological diseases.
Cancer research in India: national priorities, global results
Authors: Richard Sullivan, Rajendra A Badwe, Goura K Rath, C S Pramesh, V Shanta, Raghunadharao Digumarti, Anil D'Cruz, Suresh C Sharma, Lokesh Viswanath, Arun Shet, Manavalan Vijayakumar, Grant Lewison, Mammen Chandy, Priyadarshini Kulkarni, M R Bardia, Shaleen Kumar, Rajiv Sarin, Paul Sebastian, Preet K Dhillon, Preetha Rajaraman, Edward L Trimble, Ajay Aggarwal, D K Vijaykumar, Arnie D Purushotham
Journal: The Lancet Oncology (2014)
New Strategies for Carcinoma of Unknown Primary: The Role of Tissue-of-Origin Molecular Profiling
Authors: Gauri Varadhachary
Journal: Clinical Cancer Research (2013)

The taxonomy and management of carcinoma of unknown primary (CUP) has matured over the past decade with the use of sophisticated imaging and pathologic tools. In the era of tailored therapeutics, this presents both an opportunity and a challenge. Tissue-of-origin (ToO) molecular profiling has an important role in the diagnostic armamentarium of CUP cancers, and its niche continues to evolve with ongoing prospective studies. Despite the inability to conduct direct validation (i.e., primary tumor), the use of the indirect validation methods with immunohistochemistry (IHC), imaging, and treatment response has allowed us to evaluate the performance accuracy of ToO profiling assays in CUP cancers. Despite advances, we struggle with the undifferentiated neoplasms, which often remain unclassifiable after an exhaustive use of IHC and ToO profiling assays. Genomic characterization of these and other select CUP cancers using next-generation sequencing techniques may reveal actionable biomarkers outside the (tissue specific) cellular framework. Also, going forward, using data from comparative effectiveness research, one could envision using a streamlined, cost-effective algorithm that integrates IHC and ToO molecular profiling in patients with limited (or difficult-to-access) biopsies and difficult-to-diagnose cancers.
Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power
Authors: Josep M. Llovet, Jordi Bruix, Josep Fuster, Antoni Castells, Juan Carlos Garcia-Valdecasas, Lluís Grande, Alex França, Concepció Brú, Miquel Navasa, Maria del Ayuso, Manel Solé, Maria Isabel Real, Ramon Vilana, Antoni Rimola, Josep Visa, Joan Rodés
Journal: Hepatology (1998)

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.
Norovirus Vaccine against Experimental Human Norwalk Virus Illness
Authors: Robert L. Atmar, David I. Bernstein, Clayton D. Harro, Mohamed S. Al-Ibrahim, Wilbur H. Chen, Jennifer Ferreira, Mary K. Estes, David Y. Graham, Antone R. Opekun, Charles Richardson, Paul M. Mendelman
Journal: New England Journal of Medicine (2011)

Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection.
Review: Isolated cardiac myocytes: I Preparation of adult myocytes and their homology with the intact tissue
Authors: J. W DOW, N. G L HARDING, T. POWELL
Journal: Cardiovascular Research (1981)

Journal Article Review: Isolated cardiac myocytes: I Preparation of adult myocytes and their homology with the intact tissue Get access JOCELYN W DOW, JOCELYN W DOW * *Correspondence and reprint requests should be addressed to: Dr Jocelyn Dow, Department of Biochemistry, University of Glasgow, Glasgow, G12 QQ. Search for other works by this author on: Oxford Academic PubMed Google Scholar NIGEL G L HARDING, NIGEL G L HARDING Search for other works by this author on: Oxford Academic PubMed Google Scholar TREVOR POWELL TREVOR POWELL Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 9, September 1981, Pages 483–514, https://doi.org/10.1093/cvr/15.9.483 Published: 01 September 1981
CD40 ligand enhances monocyte tissue factor expression and thrombin generation via oxidative stress in patients with hypercholesterolemia
Authors: Valerio Sanguigni, Domenico Ferro, Pasquale Pignatelli, Maria Del Ben, Tini Nadia, Mirella Saliola, Roberto Sorge, Francesco Violi
Journal: Journal of the American College of Cardiology (2004)
Prevalence of asthma and risk factors among Chinese, Malay, and Indian adults in Singapore.
Authors: T P Ng, K P Hui, W C Tan
Journal: Thorax (1994)

BACKGROUND--The prevalence and morbidity of asthma vary greatly among different ethnic communities and geographical locations, but the roles of environmental and genetic factors are not fully understood. The differences in prevalence of adult asthma among Chinese, Malay, and Indian ethnic groups in Singapore were examined, and the extent to which these could be explained by personal and environmental factors were investigated. METHODS--A stratified disproportionate random sample (n = 2868) of Chinese (n = 1018), Malays (n = 967), and Indians (n = 883) of both sexes was drawn from households in five public housing estates, and an interviewer administered questionnaire was used to determine cumulative and current prevalence of "physician diagnosed asthma" (symptoms with a physician diagnosis of asthma). RESULTS--Lifetime cumulative prevalence (standardised to the general population) of "physician diagnosed asthma" was 4.7% in men and 4.3% in women; 12 month period prevalences were 2.4% and 2.0%, respectively. Cumulative prevalence of asthma was significantly higher in Indians (6.6%) and Malays (6.0%) than in Chinese (3.0%); period prevalences of asthma were 4.5% in Indians, 3.3% in Malays, and 0.9% in Chinese. Ownership of cats or dogs was more frequent in Malays (15.4%) and Indians (11.2%) than in Chinese (8.8%). Rugs and carpets were also more frequently used by Malays (52.2%) and Indians (40.7%) than by Chinese (8.9%). Current smoking prevalences were higher in Malays (27.3%) than in Indians (19.4%) and Chinese (23.0%). Malays and Indians did not have higher rates of atopy (11.1% and 15.2%, respectively) than Chinese (15.4%). Adjustment for these factors in multivariate analyses reduced the greater odds of asthma in Malays and Indians, but not to a significant extent. CONCLUSIONS--There are ethnic differences in the prevalence of asthma in Singapore which are not entirely explained by differences in smoking, atopy, or other risk factors. Other unmeasured environmental factors or genetic influences are likely to account for residual differences in the prevalence of asthma.
Subject to Payment?
Authors: Glenn McGee
Journal: JAMA (1997)

Fifty years after the world's conversation at Nuremberg about medical research abuses, Jean, a 20-year-old college senior, sits in the office of the clinical director of her university's egg donation program. He tells her about hyperovulation drugs and a short, outpatient procedure with a few risks. She daydreams about how strange it is to be talking with this man, and about how to handle the $12,000 on her Visa bill. Her mom and dad would faint if they knew about it. He is nice, she thinks. He looks professional and sounds honest. He asks more questions about her dreams and plans than have any of her professors. As Jean sips a cappuccino and reads through the consent form, she decides to take the money offered, sign on, and enroll as an egg donor in a small infertility protocol. She'll still have $8,000 worth of credit card debt, but she thinks
Should patients listen to how doctors frame messages?
Authors: G. Gigerenzer
Journal: BMJ (2014)

Different phrasing can change a neutral message to an implicit recommendation



Imagine that a patient with a serious heart disease is considering potentially lethal corrective surgery and asks you what the chances are. Your response can be framed in two different ways—five years after surgery, 90% of patients are still alive (survival frame) or 10% of patients are dead (mortality frame).

Should the patient’s decision depend on how you frame the message? Studies show that people are more inclined to consider surgery when the doctor uses the survival frame (albeit less so when decisions are real rather than hypothetical).1 Isn’t reacting differently to the two frames—called a framing effect—irrational? A 90% chance of survival and a 10% chance of mortality are logically equivalent. In their influential book, Nudge , Thaler …
THE EFFECT OF EPHEDRINE IN THE TREATMENT OF MYASTHENIA GRAVIS: SECOND REPORT
Authors: Harriet Edgeworth
Journal: JAMA (1933)

Three years ago I<sup>1</sup>published a short report of progress on the use of ephedrine in a case of myasthenia gravis. The correspondence that has developed with physicians and relatives of patients having myasthenia gravis seems to make a further report desirable. In the past three years, except for short periods when the ephedrine has been discontinued or the dose increased, for experimental purposes, I have taken a daily dose of 6/8 grain (48 mg.) of ephedrine sulphate or of ephedrine hydrochloride with slow but continuous improvement. The rate of improvement has been apparently uniform; that is, the amount of improvement during the last six months seems to have been as great as during the first six months. Larger doses give me a temporary increase in strength, but these dosages are invariably followed in two or three weeks by such adverse symptoms that I have always been compelled to
Consequences of occupational asthma
Authors: J. Cannon, P. Cullinan, A. N. Taylor
Journal: BMJ (1995)

Neonatal encephalopathy is an important clinical problem * In this study the incidence of moderate or severe encephalopathy was found to be 3-75 per 1000 live term births, with a case fatality of almost 8% * Intrapartum hypoxia, determined with tradi- tional criteria, was not the cause of neonatal encephalopathy in most cases * Signs of intrapartum fetal distress may be the first signs of pre-existing neurological abnor- mality, and events occurring in the antepartum period are an important cause of neurological abnormality in newborn infants * These results have implications for obste- tricians, paediatricians, and legal practitioners insult that lead to neonatal encephalopathy we therefore need (a) more specific markers of intrapartum insult than those currently used, (b) better antepartum and preconceptional history to reduce the problem of non-random missing data and unknown exposures, (c) a reliable assessment of the state of the fetus and its reserve towards the end of the antepartum period before starting labour, and (d) larger population based studies that may be analysed with methodologies such as path analysis3' so that hypotheses based on complex causal chains can be investigated.We thank staff in the study hospitals and all metropolitan and regional paediatricians for their cooperation.In particular we thank
The Histone Demethylase PHF8 Governs Retinoic Acid Response in Acute Promyelocytic Leukemia
Authors: Maria Francisca Arteaga, Jan-Henrik Mikesch, Jihui Qiu, Jesper Christensen, Kristian Helin, Scott C. Kogan, Shuo Dong, Chi Wai Eric So
Journal: Cancer Cell (2013)
Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency
Authors: Denise A Carbonaro, Lin Zhang, Xiangyang Jin, Claudia Montiel-Equihua, Sabine Geiger, Marlene Carmo, Aaron Cooper, Lynette Fairbanks, Michael L Kaufman, Neil J Sebire, Roger P Hollis, Michael P Blundell, Shantha Senadheera, Pei-Yu Fu, Arineh Sahaghian, Rebecca Y Chan, Xiaoyan Wang, Kenneth Cornetta, Adrian J Thrasher, Donald B Kohn, H Bobby Gaspar
Journal: Molecular Therapy (2013)

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA(-/-) mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA(-/-) mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34(+) cells transduced with 1-5 × 10(7) TU/ml had 1-3 vector copies/cell and expressed 1-2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis.
Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?
Authors: Tuan H. Vu, Kurenai Tanji, Stephen A. Holve, Eduardo Bonilla, Ronald J. Sokol, Russell D. Snyder, Stephany Fiore, Gail H. Deutsch, Salvatore DiMauro, Darryl De Vivo
Journal: Hepatology (2001)

Navajo neurohepatopathy (NNH) is an autosomal recessive disease of full–blooded Navajo children living in the Navajo Reservation of southwestern United States. Clinical features of NNH include peripheral and central nervous system involvement, acral mutilation, corneal scarring or ulceration, liver failure, and metabolic and immunologic derangement. The cause of NNH is unknown, but the clinical features of NNH are similar to those of patients with mitochondrial DNA (mtDNA) depletion. Therefore, we studied mtDNA concentration in the liver from 2 patients with NNH. Using histochemical, biochemical, and molecular techniques, we found evidence of mtDNA depletion, and we propose that the primary defect in NNH is in the nuclear regulation of mtDNA copy number.
Desacetylmethylcolchicine in Acute Gouty Arthritis
Authors: Jacob Colsky, Stanley Wallace, Morris M. Banowitch
Journal: New England Journal of Medicine (1955)

COLCHICINE has been the drug of choice for the treatment of patients with attacks of acute gouty arthritis because it usually causes prompt and effective symptomatic relief.1 , 2 Despite its dramatic, favorable effect in ameliorating the symptoms of this acute arthritis, it may cause gastrointestinal disturbances such as nausea, vomiting and diarrhea, or a combination of these symptoms, which are so severe in some patients as to prevent its use.Recent investigations with derivatives of colchicine have shown that although these compounds may retain potent antimitotic activity they produce less systemic toxicity in normal and tumor-bearing mice.3 4 5 6 A natural alkaloid, differing . . .
Metformin and Insulin in Type 1 Diabetes
Authors: Laurent Meyer, Bruno Guerci
Journal: Diabetes Care (2003)

Results from a population-based survey Our objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey.Details of the sampling procedures have been previously described (3).The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period.For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults).The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574).After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively.The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.The number of abnormal cases was lower using the WHO criteria.Only 237 of the 545 subjects (43.4%) who fulfilled the NCEP criteria were diagnosed as affected using the WHO definition.Just 16 of 253 cases (6.3%) detected by the WHO definition did not fulfill the NCEP definition.The agreement between the criteria was moderate ( ϭ 0.507).On the other hand, the subjects diagnosed using the WHO recommendations had a worse profile than the cases detected by the NCEP-III definition only-they had a higher BMI and higher non-HDL cholesterol, triglyceride, and glucose concentrations.The demonstration of insulin resistance among the nondiabetic population caused the lack of agreement in 202 of the 242 cases that fulfilled the NCEP definition but failed the WHO criteria.Other reasons for disparity were the higher thresholds used by the WHO criteria; these differences explained the lack of agreement in 66 of the 152 cases with diabetes.In conclusion, the prevalence of the metabolic syndrome is influenced by the selection of the diagnostic criteria.The WHO criteria identified a lower number of cases than the NCEP-III definition.These differences were explained mainly by the inclusion of abnormally high insulin concentrations as a diagnostic criterion.However, the presence of insulin resistance may help to identify patients more severely affected (4).
Primary Natural Killer-Cell Lymphoma of the Gastrointestinal Tract
Authors: H. W. Chung, S. J. Lee, S. W. Park, S. Y. Song, J. B. Chung, J. K. Kang
Journal: Endoscopy (2004)

Figure 1 A 70-year-old woman was admitted with lower abdominal pain. An 8-cm mass was palpable in the left lower quadrant of the abdomen. Abdominopelvic computed tomography showed irregular thickening of the small bowel on the left side of the abdominal cavity.