tbuckley/cabot-search huggingface dataset:
A new resource to accelerate translational breast cancer research: The Love/Avon Army of Women.
Authors: S. M. Love
Journal: Journal of Clinical Oncology (2010)

TPS115 Background: While many studies are done in cell lines and laboratory animals, translation of findings to women often falters due to perceived difficulty in recruiting women for research. The Dr. Susan Love Research Foundation (DSLRF) partnered with the Avon Foundation to form the Love/Avon Army of women (AOW) to recruit one million women interested in participating in breast cancer research as a resource for translational research. Methods: Researchers interested in having the AOW recruit for their studies, submit a proposal to be reviewed by the AOW Scientific Advisory Committee. After acceptance, a mass e-mail describing the study procedures and inclusion/exclusion criteria is sent to the entire AOW database. Women sign up online at www.armyofwomen.org to become an AOW member, agreeing to receive AOW e-mails about research studies. If an individual responds as being interested and qualified, she undergoes a secondary screening online prior to her contact information passed on to the principal investigator. As of February 2010, over 327,000 women have joined including survivors, those who have not been diagnosed with breast cancer, as well as those with and without a family history of breast cancer, ranging from ages 18 to 100, representing all 50 US states and 47 countries. To date, the AOW has recruited for 20 studies, regional and national, varying from biomarker research to quality of life studies. The AOW diversity been key to enrolling African American women, lesbians, or young survivors. Many studies were closed to enrollment within the first 24 hours while others were very quickly over-enrolled by 5-10% proving that the AOW is both efficient and effective. This overwhelming response has led many researchers to seek additional funding to increase their statistical power and accommodate all eligible subjects. Conclusions: The Love/Avon Army of Women is a novel resource for scientists to accelerate accrual, expand the number and diversity of their subject population, and to obtain exactly the type of specimens they need when they need it. This new partnership between women and scientists can revolutionize research and accelerate efforts to eradicate breast cancer. No significant financial relationships to disclose.
Dynamic control of hypercapnia level in COPD patients with sleep-disordered breathing
Authors: Liudmyla Iashyna, Yuriy Feshchenko, Svitlana Opimakh
Journal: European Respiratory Journal (2014)

Introduction: The treatment of hypercapnic chronic obstructive pulmonary disease (COPD) patients with concomitant sleep-disordered breathing (SDB) starts with continuous positive airway pressure (CPAP-therapy) under the control of the hypercapnia level in order to correct therapeutic optionsin the case of hypercapnia worsening.

Aim: To evaluate the possibility of capnometry in efficacy and safety control of CPAP-therapy in COPD patients with SDB and hypercapnia.

Methods: 10 hypercapnic COPD patients combined with obstructive sleep apnea (8 persons) or obesity hypoventilation syndrome (2 persons) received CPAP-therapy. Capnometry before and after 10 treatment nights was performed. Expired CO2 fraction (FECO2) and end-tidal CO2 fraction (FETCO2) were evaluated. The minimal clinically important difference (MCID) for FETCO2 was calculated. Data are presented as mean±SD.

Results : After CPAP-therapy we observeda statistically significant CO2 level reductionin the exhaled air: FECO2 decreased from (4.46±0.39)% to (3.71±0.46)%, FETCO2 from (6.40±0.62)% to (5.63±0.73)%, p<0.01, which means lower the degree of hypercapnia in patients. The therapy was sufficiently safe,without CO2 accumulation. The MCID for FETCO2 by the way of the standard error of measurement calculation is 0.31%, which incidentally coincides with other concept that half of the baseline standard deviation is a measure of MCID.

Conclusions: Capnometryas a simple procedure may be a useful additional tool to control efficacy and safety of CPAP-therapy in COPD patients with SDB and hypercapnia. The minimal clinically important difference for FETCO2 is 0.31%.
Nonsteroidal anti-inflammatory–induced inhibition of signal transducer and activator of transcription 6 (STAT-6) phosphorylation in aspirin-exacerbated respiratory disease
Authors: Rohit K. Katial, Michael Martucci, Trever Burnett, Anna Faino, Lindsay Finkas, Sucai Liu, Rafeul Alam
Journal: Journal of Allergy and Clinical Immunology (2016)
Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer
Authors: J. Horiguchi, Y. Koibuchi, T. Yoshida, K. Iijima, T. Oyama, Y. Iino, Y. Morishita
Journal: Journal of Clinical Oncology (2005)

900 Background: The purpose of this study is to analyze whether or not inter-site variation types on ER and HER2 expression may be a predictive factor for evaluating effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. Methods: A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER2 according to the HercepTest. In ER-positive and HER2-positive tumors, expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2 antibody. Results: Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER...
Do we need specialist units for adolescents in hospitals?
Authors: S. Sawyer
Journal: BMJ (2001)

European consensus on cancer screening should be applied urgently by health ministersEditor-In Vienna in November 1999 consensus was reached on European recommendations for cancer screening at a conference organised by the European Commission of experts in research, health care, and cancer screening from all member states of the European Union.Despite this agreement, however, the political authorities concerned have not yet officially validated the recommendations.This lack of a European policy will lead to a continuation of inefficient opportunistic screening in several member states.It will also increase the risk of uncontrolled penetration of new screening methods from commercial lobbying.This issue needs therefore to be high on the agenda of one of the next meetings of the European health ministers, preferably during Belgium's presidency of the European Union (July-December 2001).The guidelines were published in the European Journal of Cancer and will be included in the updated European Guidelines for Quality Assurance in Mammographic Screening. 1 2 They recommend that cancer screening be offered only in organised programmes with quality assurance at all levels, as well as good information about benefits and risks.The benefits of a screening programme are achieved only if coverage is high and standards of rigorous quality assurance are respected.Management and evaluation of the programme require accurate monitoring of data.Opportunistic screening activities should be discouraged as they may not achieve the potential benefits but result in negative side effects.The guidelines address screening for cervical, breast, and colorectal cancer.Pap smears should be used for cervical screening among a core age group of women aged 30-60, and the screening interval should be three to five years.If resources are available, screening could be offered to a wider age group but not to women younger than 20.Mammography should be used in screening for breast cancer, and only women aged 50-69 should be invited every two to three years.Screening for colorectal cancer by faecal occult blood detection should also be considered a preventive measure, targeting people aged 50-74 every one to two years.Immunological tests and flexible sigmoidoscopy should be evaluated as potential new tests in screening for colorectal cancer. 1 3 Screening is currently not recommended for any other form of cancer.New technologies can be introduced only after their effectiveness and cost effectiveness have been established.Use of human papillomavirus DNA detection may improve management of women with equivocal Pap smears. 4But there is insufficient evidence about the long term effects of primary screening for human papillomavirus. 5Resources should be made available to extend current population trials and increase their size, as well as to initiate new trials.European coordination of these initiatives is recommended.
Brain Natriuretic Peptide Overrides the Effects of Systemic Inflammation and Globally Increases Adiponectin Biosynthesis in Human Adipose Tissue of Patients With Ischaemic Heart Disease
Authors: A S Antonopoulos, R Patel, M Margaritis, J Digby, M Petrou, R De Silva, R Sayeed, D Tousoulis, K M Channon, C Antoniades
Journal: Circulation (2013)

Background: Regulation of adiponectin (AdN) biosynthesis in human adipose tissue (AT) is poorly understood. Pro-inflammatory cytokines suppress AdN expression in cell models, while brain natriureti...
Histopathological assessment of anastrozole versus tamoxifen as preoperative treatment in postmenopausal women with T2–4b, N0–2, M0 breast cancer: Results from a randomized, double-blind study
Authors: H. Tsuda, M. Kurozumi, F. Akiyama, G. Sakamoto, S. Noguchi, Y. Takatsuka, T. Watanabe, S. Imoto, H. Inaji
Journal: Journal of Clinical Oncology (2005)

570 Background: The PReOperative Arimidex Compared to Tamoxifen (PROACT) trial has shown that preoperative (neoadjuvant) anastrozole (A) is an effective presurgical treatment for postmenopausal women with T2–4b, N0–2, M0 hormone receptor-positive (HR+) breast cancer (n=451). Here we evaluate the histopathological response, an assessment critical to the patients’ prognosis, at the end of the presurgical period in the Japanese cohort of this study (n=97). Methods: Postmenopausal women with large operable (T2 [≥3 cm], T3, N0–2, M0) or potentially operable (T4b, N0–2, M0), estrogen receptor-positive and/or progesterone receptor-positive breast cancer were randomized to 3 months’ preoperative A 1 mg/day (n=48) or tamoxifen (T) 20 mg/day (n=49). The primary endpoint was the histopathological response derived by comparing a specimen collected at baseline with one collected 3 months after preoperative therapy. The response was evaluated on a 5-grade categorical scale (Grade 0, 1a, 1b, 2 and 3) according to the Japanese Histopathological Criteria for Assessment of Therapeutic Response in Breast Cancer by the Central Pathological Review group. A response was defined as ≥Grade 1b (i.e. a degenerative change in ≥1/3 of constituent carcinoma cells); the main outcome was an assessment of the invasion area. Results: The histopathological response rates in the intent to treat (ITT) population were 35.4% (17/48; 95% confidence interval [CI] 22.2% to 50.5%) for A and 12.2% (6/49; 95% CI 4.6% to 24.8%) for T. This was supported by the per-protocol analysis (response rate: 37.0% [n=43] vs 13.6% [n=42], respectively). The histopathological response in the ITT population was consistent with the clinical objective tumor response in 64.9% (63/97) of patients. Conclusions: A numerically higher histopathological response rate was observed with A compared with T. The histopathological and clinical response was consistent in about two-thirds of patients. These results support the main PROACT study in that A represents an effective preoperative endocrine treatment for postmenopausal women with HR+ breast cancer. No significant financial relationships to disclose.
Is overall survival an appropriate endpoint in early breast cancer studies? Data from the ATAC study at 100-month median follow-up
Authors: A. U. Buzdar, J. Cuzick
Journal: Journal of Clinical Oncology (2008)

552 Background: As the length of follow-up increases, competing causes of death are a major confounder of survival findings in studies of women with early breast cancer. Recent data from women with node-negative, estrogen receptor-positive primary breast cancer treated with adjuvant tamoxifen reported a five-fold higher risk of dying from causes other than breast cancer (Hanrahan et al. J Clin Oncol 2007; 25: 4952–60). At 100-month median follow-up in the ATAC trial, statistically significant reductions in recurrences and an advantage in disease-free survival were observed for patients treated with initial adjuvant anastrozole (A) compared with tamoxifen (T). However, no statistically significant difference in overall survival (OS) was noted. Methods: Key OS and efficacy data from the hormone receptor-positive population in ATAC at 100-month median follow-up, mean age 72 years, are presented. Results: There was significant advantage in time to recurrence in the anastrozole group (HR 0.76 [95 % CI 0.67–0.87], p=0.0001) and a 16% lower risk of distant recurrence (HR 0.84 [95 % CI 0.72–0.97], p=0.022) but no statistically significant difference was found in OS between treatment groups (HR 0.97 [95% CI 0.86–1.11], p=0.7). The number of deaths in each group was similar (A 18.0%; T 18.4%). In both groups death without recurrence (DWR) accounted for nearly half of these (A48%, T44%). From the 33-month analysis to the 100-month analysis, there was a greater increase in DWR in both groups than in deaths following recurrence. Conclusions: The impact of treatment on OS is confounded by the increasing number of deaths from other causes. Time to distant recurrence is the best measure of breast cancers that would lead to death without intercurrent intervention and should be used in preference to OS. With initial adjuvant anastrozole treatment, a greater proportion of patients avoid disease recurrence and the need for subsequent intervention. New data with respect to competing causes of mortality and survival findings in the study will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Genentech, Pfizer AstraZeneca, Eli Lilly, Genentech, Pfizer, Roche, Taiho
Randomized phase II study of concurrent and sequential combinations of rituximab (R) plus CHOP (R-CHOP) in untreated indolent B-NHL: 7-year follow-up results
Authors: K. Itoh, T. Igarashi, M. Ogura, Y. Morishima, T. Hotta, T. Kinoshita, Y. Ohashi, T. Watanabe, K. Tobinai
Journal: Journal of Clinical Oncology (2008)

8616 Background: R-CHOP is regarded as one of the most effective initial treatments for indolent B-cell Non-Hodgkin lymphoma (B-NHL); however, the information on its long term outcome is limited. Methods: Sixty-nine patients (pts) with untreated indolent B-NHL of advanced stages were randomized in the concurrent or sequential combinations of R-CHOP. Pts in the concurrent arm (Arm C) received 6 times of R (375 mg/m2), 2 days prior to each cycle of CHOP, and pts in the sequential arm (Arm S) received weekly 6 times of R (375 mg/m2) following 6 cycles of CHOP. No maintenance therapy was given in both arms. The last pt was enrolled in July, 2000, and the planned observation was completed in May, 2007. Results: A total of 69 pts were randomized but 2 were withdrawn before receiving treatment because of neutropenia or concomitant cancer. Sixty-five pts (94%) had follicular lymphoma, and 31 pts were in low, 27 in intermediate and 11 in high risk group according to the Follicular Lymphoma International Prognostic Index, respectively. We previously reported that overall response rate (ORR) in Arm C was 94%, including a 66% complete response (CR) compared with 97%, including a 68% CR in Arm S, and the time to achieving response was shorter in Arm C than Arm S (p=0.322) (Cancer Sci 2006;97;305). The median progression-free survival (PFS) of the 67 pts was 49 months; 36 months in Arm C (n=34) and 62 months in Arm S (n=33) (p= 0.417). And at 7years the estimated probability of PFS of the 67 pts was 33% (95% CI; 22–44%); 28% in Arm C and 39% in Arm S. Three pts (Arm C, 1; Arm S, 2) died. Six pts (18%) in Arm C and 11 (33%) in Arm S were progression-free at 7 years. Overall survival (OS) of the 67 pts was 96%. During the follow-up periods, clinically significant adverse event was not observed. Conclusions: R-CHOP is a highly effective initial treatment for untreated indolent B-NHL in terms of ORR and OS. However, its long-term PFS is not good enough either in a concurrent or sequential combination, warranting further investigations on post-remission therapy after R-CHOP. No significant financial relationships to disclose.
Use of the DEPArray platform to detect, isolate, and molecularly characterize pure tumor cells from peripheral blood samples enriched using the CellSearch system.
Authors: G. Medoro, S. Gross, N. Manaresi, M. Sergio, F. Fontana, S. Gianni, A. Calanca, E. Peruzzi, M. Banzi, G. Signorini, C. Rao, J. Patel, J. Karkera, G. Giorgini, M. Mata, M. C. Connelly
Journal: Journal of Clinical Oncology (2011)

10616 Background: Circulating tumor cells (CTC) offer the potential for serially monitoring the molecular profile of a tumor. However, enrichment techniques provide a level of purity problematic for most molecular analysis methods, and do not readily provide for analysis of tumor cell heterogeneity. We evaluate the use of DEPArray (Silicon Biosystems), an automated system enabling image-based cell sorting with single-cell resolution, for CTC isolation and characterization from enriched blood samples. Methods: Experiments were carried out with healthy-donor blood (HB) collected in CellSave tubes, spiked with tumor cells (TC) and enriched on Veridex’s AutoPrep with the CellSearch Epithelial Cell Kit. DEPArray system was used for detection and multiple recoveries of single TCs (or control WBCs) and 5 cell batches. A comparison of blind enumeration results with Veridex’s CellTracks Analyzer II (CTAII) was carried out on replicate samples. Results: No TCs were detected among negative controls (n=10). TC count (normalized to sample volume analyzed) was compared sample-wise for each replicate (n=20): DEPArray/CTAII count was, on average, 100% (standard deviation = 52%). Enriched mixtures of Her2+ and Her2- TCs spiked in HB samples (n=5), were sorted by DEPArray and recovered into separate tubes. By phenotypical re-analysis no Her2+ cells were detected among the Her2- cell fraction and vice versa, neither were donor WBCs found (100% purity). KRAS-mutated, A549 cells spiked in HB were enriched and loaded on DEPArray. Individual fractions containing either 1 to 5 tumor cells or donor WBCs were sorted. Whole Genome Amplification (Ampli WGA, Silicon Biosystems), KRAS specific gene amplification and Capillary Electrophoresis sequencing were carried out. TCs successfully amplified showed only mutated KRAS, (WBCs were only wild-type). Conclusions: DEPArray achieved 100% purity, eliminating all white blood cells (WBC), in the isolation of a mixed population of tumor cell lines downstream of CellSearch enrichment. This enabled molecular profiling of pure tumor cells from whole blood spiked tumor cell lines.
Spread of the autonomous transposable element hobo in the genome of Drosophila melanogaster.
Authors: M I Galindo, V Ladevèze, F Lemeunier, R Kalmes, G Periquet, L Pascual
Journal: Molecular Biology and Evolution (1995)

The transposable element hobo has been introduced into the previously empty Drosophila melanogaster strain Hikone so that its dynamics can be followed and it can be compared with the P element. Five transformed lines were followed over 58 generations. The results were highly dependent on the culture temperature, the spread of hobo element being more efficient at 25 degrees C. The multiplication of hobo sequences resulted in a change in the features of these lines in the hobo system of hybrid dysgenesis. The number of hobo elements remained low (two to seven copies) and the insertions always corresponded to complete sequences. Our findings suggest that, despite their genetic similarities, P and hobo elements differ in many aspects, such as mobility and regulation mechanisms.
Cellular immune suppression in cancer patients and its implication for dendritic cell therapy
Authors: J. Nesselhut, D. R. Lorenzen, D. Marx, R. Y. Chang, C. Matthes, B. Hildenbrand, E. M. Schneider, T. Nesselhut
Journal: Journal of Clinical Oncology (2009)

3028 Background: The treatment of human cancer with monocyte-derived dendritic cells (MoDC) is a promising and innovative approach. However, many of the treated patients fail to respond to therapy. The reduced clinical antitumor response may be due to an inflammatory immune-suppressive tumor microenvironment. Regulatory T-cells (T-reg) and other cells with suppressive potential can promote an immune suppressive tumor microenvironment and thus play an important role in regulation of the immune response. Methods: Whole blood from n=100 cancer patients with various tumor types and from n=30 healthy donors were analysed by flow cytometry. CD4 + lymphocytes with immune suppressive potential were characterized by analysing the expression of CD25, CD39, CD127. Results: We found a significantly higher proportion of CD25 + /CD39 + and of CD25 + /CD127 low T-helper cells in the blood of cancer patients as compared to healthy donors. This may indicate two different types of T-reg involved in immune suppression in cancer patients. Treatment of patients with metronomic chemotherapy induced a down-regulation of these cells. Interestingly, we found a subpopulation of cells within the lymphocyte gate characterized by CD2 high and CD86 expression in cancer patients with very advanced stage, similar to such normally found in hemaphagocytic lymphohistiocytosis (HLH) patients characterized by exceeding high plasma concentration of IFN-g and IL-10 (Schneider et al. 2002). These cells can be down-regulated by treatment with a tetradecapeptide (Ezrin) known to act as an immune modulator with anti-viral activity leading to reduction of inflammatory cytokines. Conclusions: An efficient induction of a clinical antitumor response requires both a polarization of MoDC in a TH1 direction as well as changing an immune suppressive tumor microenvironment. For the first time, we identified HLH associated cells in advanced cancer patients. As HLH is characterized by hyperinflammation, these cells may indicate an inflammatory tumor microenvironment. Thus, anti-inflammatory therapy should be considered as co-treatment with immunotherapy with dendritic cells for down-regulation of immune suppressive cells (T-reg, CD2 high /CD86 + cells) to promote a clinical antitumor response. No significant financial relationships to disclose.