tbuckley/cabot-search huggingface dataset:
An exploratory determination of new bone markers in natural history of prostate cancer (PC) patients.
Authors: J. Ayllon, J. Medioni, R. Elaidi, F. Leviel, E. Barrascout, B. Beuselinck, F. Scotte, S. Oudard, G. Maruani, P. Houillier
Journal: Journal of Clinical Oncology (2010)

e15121 Background: PC is one of the most expanded oncologic diseases worldwide. Currently, PSA is the only biological marker able to follow PC natural history. We investigated serum and urinary bone markers (BM) that may earlier define PC evolution either in hormone naive or not and free-bone metastatic pts or not. Methods: 40 PC pts distributed in 4 groups were studied as follow: A, Non castration-refractory patients (NCRP) without distant mets; B, NCRP with distant mets; C, Castration-refractory patients (CRP) without distant mets; D, CRP with distant mets. Serum BM investigated were osteogenesis-related (Osteocalcin, procollagen amino-terminal propeptide 1 {P1NP}, bone alkaline phosphatase) and osteolysis-related (collagen carboxyterminal peptide {CTX}, carboxyterminaltelopeptide type 1 collagen {1CTP}, tartrate resistant acid phosphatase {TRAP}, osteoprotegerin, receptor/activator of nuclear factor KB ligand {RANKL}). Other markers were albumin, creatinine, parathyroid hormone, total calcium and 25- OH vitamin D3. Urinary BM studied were crosslaps and creatinine. Results: Most significant markers (univariate) were used for logistic/discriminant analysis. The most contributing markers differentiating the following strata were: (1) A vs B vs C vs D : 1CTP, creatinine, P1NP, TRAP and albumine; (2) BD vs AC: P1NP, 1CTP and RANKL (ROC: AUC=0.85); (3) AB vs CD: albumine, 1CTP, P1NP and TRAP (ROC: AUC=0.88); (4) A vs C : serum and urinary creatinine, TRAP, CTX and urinary crosslaps levels (ROC: AUC=0.98). Conclusions: New BM were investigated and P1NP seems to be a relevant marker to follow natural history of PC. P1NP could be useful to predict bone metastasis evolution and a longitudinal study is under investigation. Given the small sample used in this analysis, results should be received with caution. No significant financial relationships to disclose.
Smoking history is more predictive of survival benefit from erlotinib for patients with non-small cell lung cancer (NSCLC) than EGFR expression
Authors: G. M. Clark, D. Zborowski, P. Santabárbara, K. Ding, M. Whitehead, L. Seymour, F. Shepherd
Journal: Journal of Clinical Oncology (2005)

7033 Background: Erlotinib (E, [Tarceva]) is an orally available, reversible inhibitor of the HER1/EGFR tyrosine kinase that has recently been approved by the FDA for the treatment of patients (pts) with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. A survival advantage of E compared to placebo (P) was demonstrated in a randomized, double-blind study of 731 patients with NSCLC (Shepherd et al, Proc ASCO, 2004, Abstract 7022). In this study, submission of tumor samples for determination of EGFR expression status by immunohistochemistry (DAKO EGFR pharmDx™ kit) was optional and smoking status was collected retrospectively prior to unblinding. The results of the study showed an overall survival benefit from E. Subset analyses indicated that E was particularly effective in pts with EGFR+ tumors and in pts who had never smoked. However, controversy exists about which of these characteristics is most important, and how their interaction might impact on the efficacy of E. Methods: To address these questions, univariate and multivariate analyses of survival of the 311 pts with available EGFR status and known smoking history were performed using main effects and interactions with treatment. Results: The univariate hazard ratio (HR) of death for E relative to P was 0.74, p=0.020, for all pts in this subset. Smoking history demonstrated a marginally significant interaction with treatment, p=0.054. The HRs were 0.42 among never smokers and 0.87 for current or ex-smokers, indicating that E was beneficial in both subsets, but more effective in pts who had never smoked. The interaction between EGFR status and treatment was not significant in either univariate (p=0.199) or multivariate (p=0.127) analyses; the HRs were 0.65 for EGFR+ and 0.93 for EGFR- pts. Pts with EGFR+ tumors who never smoked had the best survival benefit from E relative to P, HR=0.28, p=0.0007. Conclusions: In summary, these data confirm a benefit from E within different subsets of pts. Never smokers and pts with EGFR+ tumors experience an enhanced benefit from E compared to P, however, smoking history is more predictive of survival than EGFR expression in pts with NSCLC treated with E. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI OSI
Preventing the Admission of Difficult Psychiatric Patients—A Questionnaire Survey
Authors: Jan Neeleman, Vik Watts
Journal: Journal of the Royal Society of Medicine (1996)

By means of a postal survey of all consultant psychiatrists (n=143) in the South East Thames Region, the authors examined factors associated with psychiatrists’ decisions to impose restrictions on certain patients’ access to admission. Twenty-two per cent of respondents reported the use of admission restrictions. Usage of this measure was associated with a local absence of psychotherapy services (OR 0.34; 95% CI 0.17–0.63) which might suggest that there is a need for more equal access to specialist psychiatric services across health districts.
DNMT3AR882H mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice
Authors: L Scourzic, L Couronné, M T Pedersen, V Della Valle, M Diop, E Mylonas, J Calvo, E Mouly, C K Lopez, N Martin, M Fontenay, A Bender, S Guibert, P Dubreuil, P Dessen, N Droin, F Pflumio, M Weber, P Gaulard, K Helin, T Mercher, O A Bernard
Journal: Leukemia (2016)
Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February–March 2006
Authors: A Gilsdorf, N Boxall, V Gasimov, I Agayev, F Mammadzade, P Ursu, E Gasimov, C Brown, S Mardel, D Jankovic, G Pimentel, I Amir Ayoub, E Maher Labib Elassal, C Salvi, D Legros, C Pessoa da Silva, A Hay, R Andraghetti, G Rodier, B Ganter
Journal: Eurosurveillance (2006)

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.
H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets
Authors: Huan-Di Liu, Ai-Jie Zhang, Jing-Jing Xu, Ying Chen, Yi-Chun Zhu
Journal: Journal of Hematology & Oncology (2016)

Our previous pilot studies aimed to examine the role of hydrogen sulfide (H2S) in the generation of endothelial progenitor cells led to an unexpected result, i.e., H2S promoted the differentiation of certain hematopoietic stem/progenitor cells in the bone marrow. This gave rise to an idea that H2S might promote hematopoiesis. To test this idea, a mice model of myelosuppression and cultured fetal liver cells were used to examine the role of H2S in hematopoiesis. H2S promoted the generation of megakaryocytes, increased platelet levels, ameliorate entorrhagia, and improved survival. These H2S effects were blocked in both in vivo and in vitro models with thrombopoietin (TPO) receptor knockout mice (c-mpl−/− mice). In contrast, H2S promoted megakaryocytes/platelets generation in both in vivo and in vitro models with TPO knockout mice (TPO−/− mice). H2S is a novel promoter for megakaryopoiesis by acting on the TPO receptors but not TPO to generate megakaryocytes/platelets.
Diagnosis and Prognosis in Colon Cancer Based on a Profile of Immune Reactivity&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: B B Lurie, D M Bull, N Zamcheck, A M Steward, R A Helms
Journal: JNCI Journal of the National Cancer Institute (1975)

An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.
<i>MYD88</i> Mutations and Response to Ibrutinib in Waldenström's Macroglobulinemia
Authors: Steven P. Treon, Lian Xu, Zachary Hunter
Journal: New England Journal of Medicine (2015)

Patients with Waldenstrom's macroglobulinemia without mutations in MYD88 tend to have a shorter median survival and a lower probability of response to ibrutinib than do those with MYD88 mutations.
L-BLP25 for unresectable stage III non-small cell lung cancer after primary chemoradiotherapy in Japanese patients: Preliminary safety results from a phase I/II study.
Authors: F. Ohyanagi, T. Horai, I. Sekine, N. Yamamoto, K. Nakagawa, M. Nishio, S. Senger, N. Morsli, T. Tamura
Journal: Journal of Clinical Oncology (2010)

e13153 Background: The innovative cancer vaccine L-BLP25 (Stimuvax; BLP25 liposome vaccine) targets the MUC1 tumor-associated antigen. L-BLP25 tolerability is acceptable and Caucasian patients with stage IIIB locoregional non-small cell lung cancer (NSCLC) who are treated with L-BLP25 tend to survive longer. We report preliminary safety data from an open-label, nonrandomized phase I study combined with a double-blind, randomized, placebo-controlled phase II study. Methods: Phase I comprises administering 6 patients with unresectable stage III NSCLC after concomitant or sequential primary chemoradiotherapy (PCRT) with L-BLP25 1000 μg s.c. once weekly for 8 weeks, followed by 1000-μg maintenance doses every 6 weeks until disease progression. A single i.v. dose of cyclophosphamide (CP; 300 mg/m2, up to 600 mg) was administered 3 days before the first vaccination. An Independent Safety Monitoring Board (ISMB) reviewed the interim safety data after 6 patients had received at least 4 doses of L-BLP25. For phase II, 168 patients will be randomized 2:1 to receive either L- BLP25 or placebo. Results: The ECOG performance status of the patients (median age, 63.5 (59–69) y; M/F: 5/1) was 0 (n = 5) or 1 (n = 1). The NSCLC stages at initial diagnosis were IIIA (n = 5) and IIIB (n = 1). One and five patients had an objective response and stable disease, respectively, after PCRT. Median (range) treatment exposure and number of vaccinations were 7.7 (4.4–13.6) weeks and 8 (5–9), respectively. No serious adverse events developed and no adverse events required discontinuation. One patient stopped treatment due to disease progression. All adverse events related to treatment were grade 1 (myalgia and arthralgia, n = 1; nausea, n = 1); those related to CP comprised dysgeusia (n = 1) and anorexia and nausea (n = 1). Serum cytokine monitoring confirmed the absence of safety concerns. Conclusions: The preliminary safety and tolerability of L-BLP25 after PCRT for unresectable stage III NSCLC in Japanese patients was acceptable. The ISMB recommended starting the phase II part of the study without restrictions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck KGaA AstraZeneca, Daiichi Sankyo, Dainippon Sumitomo Pharma Co., Ltd., Eisai, Eli Lilly Japan, Janssen Pharmaceutical, Merck Serono, Novartis, sanofi-aventis
Feedback to GPs reduces antibiotic prescribing, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Sending a letter to GPs in England who have above average antibiotic prescribing rates to give feedback on their prescribing habits reduced their antibiotic prescribing by an average of just over 3% in six months, a nationwide randomised trial shows.1

Researchers used publicly available databases to identify 1581 general practices with antibiotic prescribing rates in the top 20% for their local area. They then randomly allocated GPs in these practices to receive a letter from England’s chief medical officer about their …
Note on Comparison of Small Proportions in Large-Scale Experiments2
Authors: Donald A. Pierce
Journal: JNCI Journal of the National Cancer Institute (1977)

A statistical confidence interval procedure was given for comparison of a treatment to a control where the response of each experimental unit was binary, e.g., presence or absence of a tumor. The method was appropriate when the two sample sizes were moderately large but the number of positive responses was small. The confidence interval was for the ratio of the two response rates.
A phase I and pharmacokinetic clinical trial of oral administration of the acyclic retinoid NIK-333
Authors: T. Okusaka, H. Ueno, M. Ikeda, C. Morizane, Y. Ishiguro, T. Kosuge, K. Shimada, T. Sano, Y. Sakamoto
Journal: Journal of Clinical Oncology (2005)

3108 Background: NIK-333 is an acyclic retinoid, polyprenoic acid, that prevents recurrence of hepatocellular carcinoma (HCC) after curative treatment (New Eng J Med 334:1561). We are conducting clinical trials of NIK-333 in HCC patients (pts) in order to establish its toxicity and pharmacokinetic profiles and to reconfirm its effectiveness. Methods: This study assessed the maximum tolerated dose [MTD], dose-limiting toxicities [DLT] and PK of NIK-333 administered orally at doses ranging from 300 to 900 mg/d. Thirty-three HCC pts who were free of disease after hepatic resection or percutaneous ethanol injection and met the entry criteria were enrolled. The total daily dose was taken as a single dose (single-dosing test) followed by a week of rest and then divided into two equal doses taken after breakfast and supper given for 48 consecutive weeks (repetitive-dosing test). Pharmacokinetic (PK) samples of blood and urine were collected in the single-dosing test, and blood samples were collected on days 1, 15, 29, 57, 85, 113, 141, 169, and 336 in the repetitive-dosing test, and on days 84 and 169 in the observation period after termination of administration. Results: Twelve pts treated at the starting dose level of 300 mg/d tolerated treatment well with no DLT noted. When dose was increased to 600 mg/d, 2 of 12 pts treated had grade 3 elevation of γ-glutamyl transpeptidase experienced twice during administration as a DLT. At the final dose level of 900 mg/d, 3 of 9 pts experienced grade 3 hypertension as a DLT. As the dose was increased from 300 to 900 mg/d in the single-dosing test, the mean AUC increased from 841.3 to 4009.7 ng · hr/mL, and the mean Cmax increased from 316.1 ng/mL to 906.9 ng/mL. In the repetitive-dosing test, there was no significant difference between days 1 and 169 in mean AUC0–6hr or Cmax. Conclusions: NIK-333 was well-tolerated when administrated orally at doses up to 600mg/d for 48 weeks. Hypertension was noted as a DLT at a dose level of 900mg/d. A phase II/III study is ongoing to confirm effectiveness in preventing recurrence of HCC. No significant financial relationships to disclose.
Clinical Pathology of the Jaws.
Journal: Annals of Internal Medicine (1935)

Thoma states that this volume was written to describe in detail special work in a special field and particularly to correlate the pathologic changes that are encountered in that field with the clinical expression of disease. This aim has been accomplished most successfully. Diseases of the jaw are discussed from a variety of angles: Malformations, fractures, infections, endocrine disturbances and tumors, benign and malignant, primary or metastatic, are depicted as they involve the jaw. Each phase of diseases of the jaw is well described clinically and pathologically; brief reports of cases are frequently interpolated and help to enliven the text; the illustrations are clear and helpful, and at the end of each chapter are those references to the literature which the author considers most significant in regard to the topic under discussion. A wealth of material has been analyzed and sorted out to make up this book. Thus the volume
A phase I/II study of vaccination with autologous dendritic cells (DCs) transfected with autologous amplified tumor-derived mRNA in patients with stage IV renal cell carcinoma (RCC)
Authors: J. J. Knox, D. Ornstein, K. W. Rathmell, M. K. K. Wong, M. Jewett, J. Corcos, L. H. Finke, F. Miesowicz, C. A. Nicolette, G. Batist
Journal: Journal of Clinical Oncology (2005)

4710 Background: DCs are antigen presenting cells stimulating cell-mediated immunity by effects on both CD4+ and CD8+ T-cells. We report results of a phase I/II study of a vaccine comprised of mature autologous monocyte-derived DCs transfected with autologous amplified total tumor mRNA. Methods: A single-arm, open-label study enrolled patients with newly diagnosed metastatic RCC (excluding brain). Tumor RNA is isolated from nephrectomy specimens. DCs are generated from monocytes harvested by leukapheresis. Vaccine is given by i.d. injection of 1.2x107 cells q 2-wks x5 (induction), followed by q 4-wks x5 and boosters q 3-mo until progression. Objectives: To examine feasibility, vaccine safety, immune responses, and clinical outcomes. Results: As of Dec. 1, 2004, 22 (18M/4F) of 26 patients are enrolled and 47 vaccine doses have been given. Median age is 56.5 yr. Metastatic sites; 33% lung, 19% liver, 19% mediastinum. Fourteen pts to date have had nephrectomy, leukapheresis, vaccine produced (average of 13 vaccines per pt), and received 1st dose. Of the 14, 1 withdrew consent, 1 had PD prior to restaging, and 8 have completed induction, immune monitoring, and restaging (7 with SD at 3 months and 1 with PD). Six pts did not receive vaccine due to: rapid PD (2), inoperable tumor (1), failure to obtain RNA (3). No unexpected AEs and no vaccine related SAEs. Vaccine related AEs include injection site redness/itching, mild flu-like symptoms, headache and joint pain. Conclusions: Interim data suggest that supplying multiple sites with quality controlled autologous tumor mRNA transfected DC vaccine from a central production facility is feasible for RCC. The vaccine is well-tolerated and warrants further evaluation. Biologic activity and early clinical outcomes from the fully recruited study will be available May 05. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Argos Therapeutics
Circulating tyrosinase mRNA detection in a preclinical xenograft mouse melanoma model and in advanced melanoma patients
Authors: M. R. Gabri, V. Vazquez, L. L. Otero, M. A. Castro, G. Cinat, D. E. Gomez, D. F. Alonso
Journal: Journal of Clinical Oncology (2008)

22204 Background: Although it is still under debate, molecular detection of circulating Tyrosinase is believed to be a good prognostic marker for melanoma progression. Methods: We have designed high-affinity primers to amplify the human Tyrosinase mRNA sequence to test the value of molecular detection of circulating melanoma cells by reverse transcription-PCR. The optimization process included in vitro settings and in vivo studies in a xenograft mouse model. Results: We were able to detect Tyrosinase expression with as few as 40 pg and 1.5 pg of total RNA from SKmel human melanoma cells, using PCR and nested PCR, respectively. Human Tyrosinase expression was found in the blood of nude mice bearing s.c. SKmel tumors, and expression bands were stronger after manipulation of the tumor mass. In this melanoma model, Tyrosinase expression declined in blood 6 hours after a direct intravenous injection of SKmel cells. A preliminary study in human blood samples demonstrated a baseline positive Tyrosinase determination in 64% (16/25) of advanced melanoma patients using the RT-PCR nested assay. Baseline Tyrosinase expression was significantly associated with disease progression after 12 months, and sequential determination during follow up of the remaining disease-free patients showed a progressive increase of negative results. Conclusions: We have developed sequential in vitro and in vivo preclinical validations to improve the optimization of the detection system. Our data indicate that molecular detection of circulating Tyrosinase mRNA in advanced melanoma patients could be considered a prognostic parameter. No significant financial relationships to disclose.