tbuckley/cabot-search huggingface dataset:
Abstract P1-06-08: Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes
Authors: W Kim, Y-M Kim, W Kim, J-S Lee
Journal: Cancer Research (2016)

Abstract Background and Aim Studies of Aldehyde dehydrogenase 1 (ALDH-1) and CD44+/24- have suggested them as cancer stem cell (CSC) markers in breast cancers and the clinicopathologic and prognostic significance of these CSC markers have been widely investigated. However, expressions of CSC in metastatic axillary lymph nodes (ALN) of breast cancers have not yet been the center of interest. Therefore, the object of this study is to explore breast CSC markers CD44+CD24- and ALDH-1 in the primary breast tumor and metastatic ALNs by retrospectively analyzing the CSC expressions on metastatic tumor cells within ALN. Method 180 surgically resected breast cancers were selected and among them 165 cases had undergone sentinel lymph node (SLN) with or without non-sentinel lymph node (NSLN) dissections. 50 SLNs (30.3%) and 43 NSLNs (30.9%) had metastatic tumor cells and total of 74 cases were involved with axillary lymph node metastasis. Double immunohistochemistry of CD44/CD24 and single immunohistochemical staining of ALDH-1 were applied on paraffin embedded breast tissue specimens and lymph node specimens to evaluate the CSC phenotypes of primary tumor and metastatic lymph nodes. Results The prevalence of CD44+/CD24- and ALDH-1(+) tumor cells in primary breast cancer was 76.7% and 45.0%. In triple negative breast cancers (TNBC) contained significantly higher percentage (49.2%) of ALDH-1 positive tumor cells (p=0.001). CD44+/CD24- phenotype was present in 65.2% and 40.0% in metastatic SLNs and NSLNs, respectively. The analysis of metastatic sentinel lymph nodes and breast cancers with CSCs indicated that there are significant relationships with ALDH-1(+) (p&amp;lt;0.001) and CD44+/CD24- (p&amp;lt;0.001) phenotypes. CSC expression in metastatic NSLNs and breast tumors also showed significant association (p=0.001). However, CSCs in metastatic SLNs and NSLNs did not show any significant relationships to the intrinsic molecular subtypes. Conclusions This study investigated the impact of the stem/progenitor phenotype defined by CD44 positivity/CD24 negativity and ALDH-1 positivity in sentinel lymph nodes (SLN) on non-sentinel lymph node (NSLN) metastases. CSC phenotypes expressed in metastatic SLNs and NSLNs, independently showed significant association with the primary breast tumors. However, in future, the authors recommend that the exploration of a much larger study including a vast amount of pool will provide a more reliable result. Citation Format: Kim W, Kim Y-M, Kim W, Lee J-S. Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-06-08.
Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding
Authors: Haojun Chen, Guohao Wang, Lixin Lang, Orit Jacobson, Dale O. Kiesewetter, Yi Liu, Ying Ma, Xianzhong Zhang, Hua Wu, Lei Zhu, Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2015)

The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs.
Achievements of the Belgian Antibiotic Policy Coordination Committee (BAPCOC)
Authors: H Goossens, S Coenen, M Costers, S De Corte, A De Sutter, B Gordts, L Laurier, M J Struelens
Journal: Eurosurveillance (2008)

A Belgian Antibiotic Policy Coordination Committee (BAPCOC) was officially established in 1999 by Royal Decree. The overall objective of BAPCOC is to promote judicious use of antibiotics in humans and animals and to promote infection control and hospital hygiene, with the overall aim to reduce antibiotic resistance. BAPCOC fostered strong and interdisciplinary public health, scientific and political leadership, which led to many evidence-based interventions such as multimedia campaigns to promote the prudent use of antibiotics in the community, national campaigns to promote hand hygiene in hospitals, publication of clinical practice guidelines, staffing and technical support for establishment of antibiotic management teams in all Belgian hospitals, surveillance programmes on antibiotic use and resistance in humans and animals and the promotion of research. These activities and interventions resulted in a measurable decrease in antibiotic use and resistance in the community and hospitals.
Activity of Cyclosporin A and a Non-Immunosuppressive Cyclosporin Against Multidrug Resistant Leukemic Cell Lines
Authors: W N Hait, J M Stein, A J Koletsky, M W Harding, R E Handschumacher
Journal: Cancer Communications (1989)

Cyclosporin A (CsA) has been shown to increase the sensitivity of multidrug resistant (MDR) cells to chemotherapeutic agents. Although the concentration of drug required to produce this effect is clinically achievable, the use of this drug would be hampered by significant immunosuppression. We report a comparison of the effects of 11-methyl-leucine cyclosporin (11-met-leu CsA), a non-immunosuppressive homolog to the parent drug, on MDR cell lines. Both cyclosporins sensitized resistant cell lines to doxorubicin, including P388 murine leukemia and GM 3639 human T-cell leukemia. The action of the cyclosporins was more pronounced with resistant cells than with sensitive ones. 11-Met-leu CsA was less potent than, but equally effective as, the parent drug. Both agents increased the intracellular accumulation and retention of doxorubicin in MDR cells. The sensitization caused by the cyclosporins was independent of their effects on cyclophilin, calmodulin, and protein kinase C. Furthermore, there were no differences in the binding of labelled CsA to MDR cells compared to the binding to sensitive cells, suggesting that P-glycoprotein was also not the molecular site of action. These studies demonstrate that a non-immunosuppressive cyclosporin can modulate multidrug resistance and suggest its further evaluation for use in clinical trials.
Adrenergic coronary vasoconstriction during myocardial underperfusion.
Authors: Feigl Eo, Buffington Cw, Nathan Hj
Journal: Circulation (1987)

The effects of adrenergic alpha-receptor-mediated coronary vasoconstriction were examined in the presence of coronary stenosis and during experimental coronary hypoperfusion. Adrenergic coronary vasoconstriction was observed to operate even in the presence of coronary stenosis to limit oxygen delivery to the heart and increase myocardial oxygen extraction, but this vasoconstrictor effect did not result in myocardial lactate production. During constant coronary pressure perfusion the transmural distribution of alpha-receptor coronary vasoconstriction was determined with microspheres. A uniform transmural distribution of alpha-receptor-mediated vasoconstriction was observed at normal and subnormal perfusion pressures. During constant flow hypoperfusion, which permits transmural coronary steal, the left ventricular inner/outer blood flow ratio was more favorable with alpha-receptors intact than with alpha-receptors blocked. These findings indicate that alpha-receptor-mediated coronary vasoconstriction has an unexpected beneficial effect by lessening transmural steal during coronary hypoperfusion.
Congenital Cytomegalovirus Infection
Authors: K L Tan, A Wee, S Doraisingham
Journal: New England Journal of Medicine (1982)

Three cases of overt congenital cytomegalovirus infection, each with a different mode of presentation, are documented. Common features of presentation were hepatosplenomegaly, skin petechiae, neonatal jaundice and gross hepatic dysfunction. One infant presented with hydrops fetalis, a feature not described before. Two infants survived and are at present developing normally.
Surveillance of Lyme borreliosis in Germany, 2002 and 2003
Authors: W H Mehnert, G Krause
Journal: Eurosurveillance (2005)

Lyme borreliosis is a potentially serious infection common in Germany, but little data about its incidence, distribution, and clinical manifestations are available. Lyme borreliosis is not a notifiable disease in Germany, but six of Germany's 16 states - Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt and Thüringen, have enhanced notification systems, which do include Lyme borreliosis. The efforts made in these states to monitor confirmed cases through notification are therefore an important contribution to understanding the epidemiology of Lyme borreliosis in Germany. This report summarises the analysis of Lyme borreliosis cases submitted to the Robert Koch-Institut during 2002-2003. The average incidence of Lyme borreliosis of the six East German states was 17.8 cases per 100,000 population in 2002 and increased by 31% to 23.3 cases in 2003, respectively. Patient ages were bimodally distributed, with incidence peaks among children aged 5- 9 and elderly patients, aged 60- 64 in 2002, and 65- 69 in 2003. For both years, 55% of patients were female. Around 86% of notified cases occurred from May to October. Erythema migrans affected 2697 patients (89.3%) in 2002 and 3442 (86.7%) in 2003. For a vector-borne disease, like Lyme borreliosis, the risk of infection depends on the degree and duration of contact between humans and ticks harbouring Borrelia burgdorferi. As infectious ticks probably occur throughout Germany, it is likely that the situation in the remaining 10 German states is similar to that of the states in this study.
The dexamethasone suppression test in residual schizophrenia with depression
Authors: J G Munro, T M Hardiker, D P Leonard
Journal: American Journal of Psychiatry (1984)

The authors administered the Carroll rating scale for depression to 100 patients with residual schizophrenia and found that 41 were also depressed. Of these 41 patients, 23 were given a dexamethasone suppression test; 7 (31%) failed to suppress cortisol. A matched control group, i.e., 23 patients with residual schizophrenia but without depression, suppressed cortisol normally after taking dexamethasone. The authors found no clinical differences between depressed patients with normal DST results and depressed patients with abnormal DST results.
Establishment of a Clone of Mouse Liver Cells from a Single Isolated Cell
Authors: Gwendolyn Likely Hobbs, Katherine K. Sanford, Virginia J. Evans, Wilton R. Earle
Journal: JNCI Journal of the National Cancer Institute (1957)

Establishment of a Clone of Mouse Liver Cells from a Single Isolated Cell Get access Gwendolyn Likely Hobbs, Gwendolyn Likely Hobbs National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Katherine K. Sanford, Katherine K. Sanford National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Virginia J. Evans, Virginia J. Evans National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle Wilton R. Earle National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 5, May 1957, Pages 701–707, https://doi.org/10.1093/jnci/18.5.701 Published: 01 May 1957 Article history Received: 06 March 1957 Published: 01 May 1957
Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) –Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline
Authors: Neelima Denduluri, Mark R. Somerfield, Andrea Eisen, Jamie N. Holloway, Arti Hurria, Tari A. King, Gary H. Lyman, Ann H. Partridge, Melinda L. Telli, Maureen E. Trudeau, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2016)

A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers was identified for adaptation.The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability.On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members.Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.
Abstract OT3-01-12: Phase II trial of lapatinib and everolimus for HER2 positive metastatic breast cancer
Authors: JA Barr, P Sharma, CJ Fabian, H Yeh, S Baccaray, M Springer, QJ Khan
Journal: Cancer Research (2016)

Abstract Background: Although the treatment of HER2 positive metastatic breast cancer (MBC) has improved with anti-HER2 agents and chemotherapy, most patients will eventually develop resistance to these agents. Preclinical studies have shown that mTOR inhibition may reverse trastuzumab resistance. We hypothesize that combining mTOR inhibitor everolimus with lapatinib will be an effective strategy for patients who have progressed on prior anti-HER2 therapies. Trial Design: We are conducting an open-label phase II pilot study of the combination of everolimus and lapatinib for pts with HER-2 positive MBC. Eligible pts must have histologically documented locally advanced (inoperable) or metastatic HER-2 positive breast cancer that have progressed on at least one HER-2 based regimen in the metastatic or locally advanced setting. Pts with disease progression during or within 12 mos of the completion of adjuvant trastuzumab are eligible. Pts with untreated asymptomatic brain metastases are allowed. Pts with symptomatic brain metastases are allowed to enroll after they have completed radiation and are off steroids. Eligible pts are started on everolimus 5 mg PO daily and lapatinib 1250 mg PO daily without interruption. Among subjects progressing on lapatinib, lapatinib is continued and everolimus initiated. Pts will continue to receive treatment until there is evidence of progressive disease (PD), unacceptable toxicity, or withdrawal of consent. Pts will have radiological evaluation every 8 weeks with CT, bone scan, and MRI brain (for pts with known brain metastasis at baseline). Specific Aims: Primary objective is to assess the effectiveness of the combination of RAD-001 and lapatinib as measured by the six-month Overall Response Rate in women with MBC who have progressed on trastuzumab and/or lapatinib based therapies. Secondary objectives are six-month PFS, safety and tolerability of the combination, six-month objective CNS response rate, six-month clinical benefit rate of systemic disease, and six-month clinical benefit rate in CNS. Statistical methods: The response rate of lapatinib monotherapy in heavily pre-treated patients is estimated to be 7% (Blackwell 2009). For an expected ORR of 17%, a sample size of 45 subjects will provide 79% power to detect the difference at 0.10 Type I error rate according to 1-sided exact binomial test. Present accrual and target accrual: The trial has accrued 20 patients with a target accrual of 45 patients. Citation Format: Barr JA, Sharma P, Fabian CJ, Yeh H, Baccaray S, Springer M, Khan QJ. Phase II trial of lapatinib and everolimus for HER2 positive metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-12.
Abstract P5-14-03: A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer
Authors: C Telford, N Jones, S Batson
Journal: Cancer Research (2016)

Abstract Background A network meta-analysis (NMA) of randomized controlled trials compared overall survival (OS) and serious adverse events (SAEs) of fulvestrant 500 mg with alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. Methods Data were identified by systematic literature review. Study level hazard ratios (HRs) were obtained by modeling survival data using Weibull distribution, based on statistical and visual fit. SAEs were calculated as rate of grade 3/4 adverse events per patient year. Fixed effect Bayesian NMA were conducted for both outcomes.The base case included the following comparators of interest: anastrozole 1 mg, letrozole 2.5 mg, fulvestrant 250 mg, exemestane 25 mg, everolimus 10 mg plus exemestane 25 mg. The first three comparators were included in a subgroup analysis of treatment post-antiestrogen (antiestrogen subgroup), the last three were included in a subgroup analysis of treatment post-aromatase inhibitor (aromatase inhibitor subgroup). Results Ten studies were included; all studies reported SAEs, 7 studies reported OS. In the base case, fulvestrant 500 mg improved OS versus all comparators and in the antiestrogen subgroup versus fulvestrant 250 mg (HR 0.74; 95% credible interval [CrI] 0.56, 1.00), anastrozole (HR 0.73; 95% CrI 0.52, 1.03), and letrozole (HR 0.69; 95% CrI 0.44, 1.09). In the aromatase inhibitor subgroup, fulvestrant 500 mg improved OS versus fulvestrant 250 mg (HR 0.89; 95% CrI 0.59, 1.33) and exemestane (HR 0.93; 95% CrI 0.58, 1.47); OS for fulvestrant 500 mg versus everolimus plus exemestane was similar (HR 1.02; 95% CrI 0.62, 1.69). Decreased SAE rates were seen for fulvestrant 500 mg versus letrozole, exemestane, and everolimus plus exemestane (13.22 versus 20.65, 46.63, 67.30 events, respectively) in base case and versus fulvestrant 250 mg and letrozole (14.88 versus 15.67, 23.41 events, respectively) in the antiestrogen subgroup. NMA in the aromatase inhibitor subgroup was not performed (lack of reporting SAEs). Conclusions This analysis suggests improved efficacy for fulvestrant 500 mg versus fulvestrant 250 mg and aromatase inhibitors, similar efficacy to everolimus plus exemestane, and decreased toxicity amongst a majority of the comparators. Fulvestrant 500 mg can be considered an efficacious and better tolerated alternative endocrine treatment in this setting. Citation Format: Telford C, Jones N, Batson S. A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-03.
Effect of pindolol in hastening response to fluoxetine in the treatment of major depression: a double-blind, placebo-controlled trial
Authors: R M Berman, A M Darnell, H L Miller, A Anand, D S Charney
Journal: American Journal of Psychiatry (1997)

In two preliminary studies, pindolol produced robust results in hastening clinical response to antidepressant drugs in depressed patients. Validity of those pilot studies was limited by use of an open-label, unblinded study design, and so the authors conducted a double-blind, placebo-controlled trial to assess the effectiveness of pindolol in hastening response to fluoxetine.Drug-free outpatients with major depression were concurrently treated with fluoxetine (20 mg/day) and either placebo or pindolol (5.0 mg b.i.d. or 2.5 mg t.i.d.), for 6 weeks, in a randomized, double-blind manner. After 6 weeks, all patients received fluoxetine and placebo and were followed for 3 further weeks in a single-blind manner.Forty-three patients completed at least 1 week of the protocol. Rates of partial remission after 2 weeks of treatment with fluoxetine and either pindolol or placebo were 17% (four of 23 patients) and 20% (four of 20 patients), respectively. At study completion, 65% of the patients (N = 28) demonstrated at least a partial remission, and there was no difference between treatment groups. The pindolol group, but not the placebo group, demonstrated significant reductions in blood pressure and pulse rate. The average time to remission and the rates of attrition, overall response, and side effects were similar in the two groups.These findings do not support the efficacy of pindolol in hastening clinical response in patients treated with fluoxetine.
Women in Ulster should have access to abortion services
Authors: L. Beecham
Journal: BMJ (2003)

Representatives at the BMA's annual conference criticised the fact that women in Northern Ireland still do not have access to the same abortion facilities as women in the rest of the United Kingdom and called on the government to rectify this anomaly.

When abortion was legalised in Britain in 1967 the Abortion Act it did not cover Northern Ireland, and …
What comes after standardised packaging for tobacco?
Authors: Nicholas S Hopkinson
Journal: BMJ (2016)

The industry should pay a levy to provide sustainable funding for tobacco control policies

The tobacco industry is on course to kill around one billion people in the 21st century,1 with a global social burden costing an estimated $2.1tr a year.2 Smoking related disease remains the number one cause of preventable deaths in the UK. The implementation of regulations for standardised packaging of tobacco products on 20 May in the UK and France, with Ireland soon to follow, therefore represents an important step forward for public health. These “plain packs” will be a drab brown colour, with product branding restricted to the name as text in a standard font. The revised EU Tobacco Products Directive, which is being implemented at the same time, contains additional requirements such as minimum pack sizes, larger combined picture and text health warnings to cover 65% of the front and the back of packets, and prohibition of characterising flavours, including menthol, from 2020. …