tbuckley/cabot-search huggingface dataset:
Maintenance Treatment with Cetuximab and BAY86-9766 Increases Antitumor Efficacy of Irinotecan plus Cetuximab in Human Colorectal Cancer Xenograft Models
Authors: Teresa Troiani, Stefania Napolitano, Giulia Martini, Erika Martinelli, Claudia Cardone, Nicola Normanno, Donata Vitagliano, Floriana Morgillo, Francesca Fenizia, Matilde Lambiase, Luigi Formisano, Roberto Bianco, Davide Ciardiello, Fortunato Ciardiello
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The use of cetuximab in the treatment of metastatic colorectal cancer is limited by development of resistance. Experimental Design: We have investigated in three models of highly epidermal growth factor receptor (EGFR)–dependent colorectal cancer xenografts, the effect of maintenance therapy with different kinase inhibitors alone or in combination with cetuximab, after cytotoxic treatment induction with irinotecan plus cetuximab. Results: SW48, LIM 1215, and GEO colorectal cancer cell lines were engrafted into nude mice and treated for 3 weeks with irinotecan and/or cetuximab. The combined treatment induced a significant reduction of tumor size. A subsequent experiment was performed in all three xenograft models in which after an induction treatment with irinotecan plus cetuximab, mice were randomly assigned to one of the following treatments: control, cetuximab, regorafenib, a selective PIK3CA inhibitor (PIK3CAi), a selective MEK inhibitor (MEKi), and/or the combination of each inhibitor with cetuximab. The cetuximab plus MEKi treatment determined the best antitumor activity with suppression of tumor growth. This effect was prolonged for 13 to 15 weeks after cessation of therapy and was accompanied by prolonged survival. Antitumor activity was accompanied by inhibition of the MAPK and MEK pathways. Moreover, in the cetuximab plus MEKi-treated SW48 xenograft group, KRAS mutations as a mechanism of acquired resistance were detected in 25% of cases compared with 75% KRAS mutations in the MEKi-treated group. Conclusions: A possible strategy to prevent and/or overcome resistance to anti-EGFR inhibitors in metastatic colorectal cancer is a maintenance therapy with cetuximab plus MEKi after an initial treatment with irinotecan plus cetuximab. Clin Cancer Res; 21(18); 4153–64. ©2015 AACR.
The performance of flow cytometry in the diagnosis of latent tuberculosis infection in patients under treatment with anti-TNFa and other biological agents
Authors: Chrysovalantis Papageorgiou, Maria Ploussi, Simona Karabela, Kyriakos Fotiadis, Andreas Anastasopoulos, Apostolos Papavasileiou, Evangelos Vogiatzakis, Dimitrios Ioakeimidis, Angelos Gritzapis, Nikolaos Poulakis
Journal: European Respiratory Journal (2013)

Introduction: Detection of IFN-γ synthesis in the cytoplasm of activated CD4+ T cells by flow cytometry [intracellular cytokine flow cytometry (ICCFC)] is a new method to diagnose tuberculosis (TB) infection. The aim of this study is to investigate the performance of Mantoux, Quantiferon Gold In-tube (QFN-G-IT) and ICCFC in patients with collagen vascular diseases who are on treatment with biological agents, including anti-TNFa.  Methods: Mantoux, QFN-G-IT and ICCFC were performed in 54 medically immunosuppressed patients and in a cohort of immunocompetent individuals consisting of a group of 39 close contacts with an index case of TB.  Results: In patients under anti-TNFa treatment, 28/54 (52%) were ICCFC ESAT-6 (+), compared with QFN-G-IT (+) who were 3.7% (p  Conclusion: The performance of ICCFC for the diagnosis of TB infection is better than QFN-G-IT and Mantoux in patients under immunosuppressive treatment and in immunocompetent close contacts. The robustness of ICCFC test is not substantially affected by the administration of immunosuppressive treatment.
Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first- or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial.
Authors: R. A. Dent, G. J. Lindeman, M. Clemons, H. Wildiers, A. Chan, N. J. McCarthy, C. F. Singer, E. S. Lowe, K. Kemsley, J. Carmichael
Journal: Journal of Clinical Oncology (2010)

1018 Background: Triple negative breast cancer (TNBC) shares molecular characteristics with BRCA1-/- breast cancer (BC). Preclinical and clinical data show that BRCA1-/- BC and TNBC are sensitive to inhibition of PARP1, an enzyme necessary for DNA repair and other critical cell functions. This phase 1 study evaluated the tolerability of olaparib, a potent PARP1 inhibitor, combined with weekly paclitaxel in patients with metastatic TNBC. This trial served as a safety evaluation to be followed by a phase II trial after tolerability was determined. Methods: Eligible patients (pts) had ≤ 1 prior cytotoxic regimens for ER-, PR-, and HER2- metastatic BC. Pts were treated with olaparib 200mg capsules PO BID continuously combined with paclitaxel 90mg/m2 IV weekly for 3 of 4 weeks. At this dose, a significant number of pts had delays due to neutropenia, thus a second cohort of 10 pts was enrolled with an amendment to the protocol to allow for GCSF (300 μ g SC days 3-5) as secondary prophylaxis following weekly paclitaxel to maintain dose intensity. Results: Nineteen pts were enrolled (median age 49.0 years [range 36 - 71 years]); all PS 0-1; median one prior metastatic chemo regimen; 15 pts had prior taxane chemotherapy. The most frequent (n) grade 1-2 adverse events were fatigue (10; grade 3 > 1/10), nausea (10) diarrhea (12). Grade 1-2 neutropenia was reported in 5 pts, grade 3 in 5 pts, grade 4 in 1 pt, and febrile neutropenia in 1 pt (grade 3). Neutropenia in the second cohort was managed with GCSF in 3/10 pts, but 2/3 pts had recurrent grade 2 neutropenia despite GCSF prophylaxis. Using investigator-assessed RECIST response, 7 pts (37%) had confirmed partial responses (PRs), 10 pts (53%) had confirmed+ unconfirmed PRs. Data on PFS will be presented. Conclusions: The combination of olaparib and weekly paclitaxel was well tolerated, but acceptable dose intensity (i.e., missed/delayed doses) was not achieved due to neutropenia despite secondary prophylaxis with GCSF. This preliminary analysis demonstrated promising efficacy. Alternative schedules and dosing of olaparib are being considered. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca, GlaxoSmithKline, Novartis, Roche AstraZeneca
Physiology of the female reproductive axis
Authors: G. Wright Bates, Meaghan Bowling
Journal: Periodontology 2000 (2012)

Abstract The female reproductive system contains two principal components: the uterus, which supports the developing fetus, and the ovaries, which produce the female gametes. This manuscript will review how the hypothalamus, pituitary, ovary and uterus are integrated into the female reproductive system. The endocrinology of pregnancy, as well as a cursory overview of reproductive pathology, will be presented in each section. In addition, the most common endocrinopathy in women, polycystic ovarian syndrome, as well as the early loss of reproductive function, premature ovarian failure, will receive special mention.
Male doctors are more likely to have legal action taken against them, analysis finds:
Authors: Ingrid Torjesen
Journal: BMJ (2015)

Male doctors have nearly two and a half times higher odds of having legal action taken against them than female doctors, a meta-analysis published in the open access journal BMC Medicine has found.1

Researchers from University College London identified 32 studies from around the world that had looked at medicolegal action against doctors by sex. This included disciplinary action taken against doctors by medical regulatory boards, malpractice claims and cases, complaints received …
The Genetic Activity Profile Database
Authors: Michael D. Waters, H. Frank Stack, Neil E. Garrett, Marcus A. Jackson
Journal: Environmental Health Perspectives (1991)

A graphic approach termed a Genetic Activity Profile (GAP) has been developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose (LED) or highest ineffective dose (HID) is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for the production and evaluation of GAPs has been developed in collaboration with the International Agency for Research on Cancer. Data on individual chemicals have been compiled by IARC and by the U.S. Environmental Protection Agency. Data are available on 299 compounds selected from volumes 1-50 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar GAPs. By examining the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluating chemical analogs. GAPs have provided useful data for the development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from assessing the GAPs of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines.
Integrated molecular analysis of adult T cell leukemia/lymphoma
Authors: Keisuke Kataoka, Yasunobu Nagata, Akira Kitanaka, Yuichi Shiraishi, Teppei Shimamura, Jun-Ichirou Yasunaga, Yasushi Totoki, Kenichi Chiba, Aiko Sato-Otsubo, Genta Nagae, Ryohei Ishii, Satsuki Muto, Shinichi Kotani, Yosaku Watatani, June Takeda, Masashi Sanada, Hiroko Tanaka, Hiromichi Suzuki, Yusuke Sato, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masako Iwanaga, Guangyong Ma, Kisato Nosaka, Masakatsu Hishizawa, Hidehiro Itonaga, Yoshitaka Imaizumi, Wataru Munakata, Hideaki Ogasawara, Toshitaka Sato, Ken Sasai, Kenzo Muramoto, Marina Penova, Takahisa Kawaguchi, Hiromi Nakamura, Natsuko Hama, Kotaro Shide, Yoko Kubuki, Tomonori Hidaka, Takuro Kameda, Tsuyoshi Nakamaki, Ken Ishiyama, Shuichi Miyawaki, Sung-Soo Yoon, Kensei Tobinai, Yasushi Miyazaki, Akifumi Takaori-Kondo, Fumihiko Matsuda, Kengo Takeuchi, Osamu Nureki, Hiroyuki Aburatani, Toshiki Watanabe, Tatsuhiro Shibata, Masao Matsuoka, Satoru Miyano, Kazuya Shimoda, Seishi Ogawa
Journal: Nature Genetics (2015)
Novel &amp; effective management of capecitabine induced Hand Foot Syndrome
Authors: D. Pendharkar, H. Goyal
Journal: Journal of Clinical Oncology (2004)

8105 Background: Hand foot syndrome ( Palmar plantar erythrodysesthesia ) is common side effect of capecitabine. Grade II-III toxicity is seen in 10–50%of the patients and may lead to discomfort with activities of daily living. Interruption in the treatment and dose reductions are very frequent due to this toxicity. Aim of the study was to analyze efficacy of local application of keratolytic agent - urea (12.5%) (Cotoryl R) on capecitabine induced toxicity. Methods: Patients on capecitabine were followed for signs of hand foot syndrome. Thirteen such episodes were recorded. Out of theses 4 episodes were of grade III and 9 of grade II toxicity. All had dry furrowed skin, rash, desquamation on the palms of the hands and soles of the feet. Patients with grade III toxicity had additionally painful erythema, discomfort with activities of daily living. All patients were asked to apply locally, twice a day, urea containing moisturizing ointment. The same preparation was used prophylactically in 7 cycles of capecitabine. Results: This application had a dramatic impact on dermatological complications within 2–3 days of initiation. The effect lasted till continuation of the application. It lead to reduction in desquamation, pain, and comfort level of all the patients improved. Neurological symptoms improved as well. All patients were able to complete the chemotherapy cycle as per the schedule and without interruption or delays. Efficacy was seen in patients where it was used prophylactically. 5/7 did not develop cutaneous manifestation and two had grade I toxicity. Conclusions: Urea containing preparation appears to be an excellent choice for the prevention and treatment of capecitabine induced hand foot syndrome. This minimizes drug delays, schedule interruptions and maintains the dose density. Owing to reduced morbidity, the drug tolerance and acceptance is considerably improved. No significant financial relationships to disclose.
Banking on interest
Authors: C. White
Journal: BMJ (1998)

By her own admission, Afton Blake fell madly in love with Number 28's Nordic looks, his non-competitive sporting talent, and his career in computer science. But what really clinched it for her, was his bulging IQ and healthy bank deposit at the romantically named Repository for Germinal Choice in California—a giant freezer of seminal genius for the discerning mother to be.

Afton sealed her union with Number 28 with a glinting syringe and a blaze of candlelight, and named her son Doron—Greek for gift and an anagram of donor. Now almost 16, Doron is one of a million children fathered by anonymous sperm donors since the second world war and part of a multimillion dollar industry. Amid the cradles of test tubes, fished out of billowing liquid nitrogen, and the huge canisters with their cargo of DNA in suspended animation, “Test Tube Dads” attempts to tell the human side of the story.

And it's a complex …
An alternative method to overcome central venous portable external infusion pump blockage in patients receiving weekly 24-hour high-dose fluorouracil and leucovorin.
Authors: K H Yeh, A L Cheng
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.4.875 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8151330 An alternative method to overcome central venous portable external infusion pump blockage in patients receiving weekly 24-hour high-dose fluorouracil and leucovorin. K H YehxK H YehSearch for articles by this author , A L ChengxA L ChengSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.4.875 PDF "An alternative method to overcome central venous portable external infusion pump blockage in patients receiving weekly 24-hour high-dose fluorouracil and leucovorin.." Journal of Clinical Oncology, 12(4), pp. 875–876© 1994 by American Society of Clinical Oncology
Over-reading spirometry – Man or machine?
Authors: Aleck Harrison, Grant Sowman, Hardip KaurNagra
Journal: European Respiratory Journal (2011)

The quality of spirometry improves in multicentre trials with the aid of over-reading and prompt feedback to sites [1]. Recently spirometer software has become more sophisticated with increased built-in quality control. So is there a need for human intervention?  An international trial with 519 asthmatic patients from 78 sites over 17 weeks produced 7297 spirometry sessions. The site spirometer program (Vitalograph Spirotrac®) determined the acceptability of each session with immediate feedback allowing the investigator to make decisions on the patients involvement. All sessions were e-transferred to the database and full visual inspection of the spirometry curves made by three expert over-readers with feedback within 48hrs, reading to ATS/ERS standards [2].  The shape of both curves for rejected sessions follows that seen in other trials, the slope having been demonstrated to be due to prompt feedback. In studies with no feedback the rejection rate is constant [1].  Although there were small differences, this analysis demonstrates that despite hard objective parameters built into software there still needs to be the expert quality of the over-reader9s eye.   References:   1Harrison A. Blow by Blow, Int Clin Trials J. 2009;4:68-70.  2Miller MR et al. ATS/ERS Standardisation of Spirometry, ERJ 2005;26;319.  The trial sponsors are thanked for the anonymous use of their data.
Invasive pneumococcal disease among children in a health district of Barcelona: early impact of pneumococcal conjugate vaccine
Authors: E. Calbo, Á. Díaz, E. Cañadell, J. Fábrega, S. Uriz, M. Xercavins, M.A. Morera, E. Cuchi, M. Rodríguez-Carballeira, J. Garau
Journal: Clinical Microbiology and Infection (2006)
Inducible Macrophage Cytotoxins. II. Tumor Lysis Mechanism Involving Target Cell-Binding Proteases&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Thomas H. Reidarson, Gale A. Granger, Jim Klostergaard
Journal: JNCI Journal of the National Cancer Institute (1982)

Thioglycollate-elicited G57BL/6 peritoneal exudate macrophage monolayers (PEMM) stimulated with poly I · poly C or LPS released a macrophage cytotoxin (MCT) that rapidly bound to syngeneic (EL 4) or allogeneic (NS-1, YAC-1) tumor cells but did not bind to normal splenocytes. No binding to human (K562) tumor cells was observed. PEMM stimulated with poly I · poly C destroyed allogeneic tumor cells (NS-1 ) when separated by cell-impermeable Millipore filters in vitro; in contrast, PEMM not stimulated with poly I · poly C were incapable of lysing targets when separated by membranes. The reversible inhibitors Nα-p-tosyl-L-arginine methyl ester and soybean trypsin inhibitor and the irreversible inhibitors Nα-p-tosyl-L-Iysine chloromethyl ketone and phenyl methyl sulfonyl fluoride, of trypsin-like proteases, significantly or totally inhibited MCT cell-lytic activity for L-929 cells in vitro. Furthermore, modification of MCT-associated arginine residues by 1,2-cyclohexanedione completely blocked lytic activity. MCT was concluded to be an inducible nonspecific cell-lytic effector molecule elaborated by activated macrophages, which could bind to potential target cells, and was itself or was associated with a protease.
Molecular analysis of community-acquired methicillin-susceptible and resistant Staphylococcus aureus isolates recovered from bacteraemic and osteomyelitis infections in children from Tunisia
Authors: A. Kechrid, M. Pérez-Vázquez, H. Smaoui, D. Hariga, M. Rodríguez-Baños, A. Vindel, F. Baquero, R. Cantón, R. del Campo
Journal: Clinical Microbiology and Infection (2010)
High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial.
Authors: W P Peters, J P Eder, W D Henner, S Schryber, D Wilmore, R Finberg, D Schoenfeld, R Bast, B Gargone, K Antman
Journal: Journal of Clinical Oncology (1986)

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.
A Case-Control Study of Hair Dye Use and Breast Cancer&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R E Shore, B S Pasternack, E U Thiessen, M Sadow, R Forbes, R E Albert
Journal: JNCI Journal of the National Cancer Institute (1979)

A case-control study of the relationship between hair dye use and breast cancer included 129 breast cancer patients and 193 control women drawn from the records of a multiphasic screening clinic. Information was obtained by telephone interview on a number of risk factors for breast cancer and on variables pertaining to hair dye use: chronologic time, duration, frequency, type, and color. From this, quantitative measures of cumulative hair dye use at various intervals prior to breast cancer (or an equivalent for controls) were obtained. A multivariate risk factor score was used to control for confounding variables. The adjusted relative risks for breast cancer versus hair dye use were greater than unity but were not generally significant. However, integral measures of hair dye use (No. of yr times frequency per yr) were significantly related to breast cancer when confounding variables were controlled. The association between hair dye use and breast cancer was greatest among women over 50 years of age and among those at lower natural risk for breast cancer. An analysis of temporal patterns showed that breast cancer was related mainly to hair dye use 10 or more years before cancer diagnosis. Because of the retrospective nature of the hair dye data and the small sample size, these results require further validation.
Egg and milk allergy in adults
Authors: A. Nørgaard, C. Bindslev‐Jensen
Journal: Allergy (1992)

Nineteen adult patients representing a total of 24 medical histories of immediate adverse reactions to egg or cows’ milk underwent 1) standardized questioning about signs/symptoms occurring less than 2 h after ingestion of egg or milk, 2) skin prick test, RAST and histamine release test, and 3) titrated, oral, double‐blind, placebo‐controlled challenge (DBPCFC) with fresh egg or milk. Eleven medical histories (46%) were confirmed by DBPCFC in 10 patients (53%). All DBPCFC‐positive patients experienced gastrointestinal symptoms, and in 80% of the patients, gastrointestinal symptoms were accompanied by respiratory or skin symptoms. Threshold doses varied between 50 mg and 250 g, with 4 patients presenting objective signs following 5 g or less. DBPCFC‐positive patients reported significantly more symptoms and had a significantly higher number of positive tests than had DBPCFC‐negative patients. None of the tests were in significant concordance with DBPCFC, although RAST showed a sensitivity of 100%. Thus, DBPCFC cannot be substituted in the diagnosis of milk and egg allergy in adults. The use of titrated, fresh foods in DBPCFC proved to be a safe and well‐controlled procedure.
Genotypic characterization and historical perspective of Mycobacterium tuberculosis among older and younger Finns, 2008–2011
Authors: P.W. Smit, M. Haanperä, P. Rantala, D. Couvin, O. Lyytikäinen, N. Rastogi, P. Ruutu, H. Soini
Journal: Clinical Microbiology and Infection (2014)