tbuckley/cabot-search huggingface dataset:
Randomised trial of capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (GemOx) in advanced pancreatic cancer
Authors: V. Heinemann, A. Golf, G. Seipelt, J. Bauer, T. Höhler, M. Clemens, J. M. Löhr, M. Stauch, F. Lordick, A. Hinke
Journal: Journal of Clinical Oncology (2004)

4108 Objective: To compare the efficacy and tolerability of three different combination regimens, CapOx, CapGem, and GemOx for treatment of advanced pancreatic cancer. Patients: Of 165 planned pts, 135 pts have been enrolled between June 2002 and December 2003 from 37 centres. Patients (pts) received either capecitabine 2 x 1000mg/m2 po d1–14 plus oxaliplatin 130mg/m2 iv d1 (CapOx) or capecitabine 2 x 825mg/m2 po d1–14 plus gemcitabine 1000mg/m2 iv d 1+8 (CapGem) or or gemcitabine 1000 mg/m2 iv d1+8 plus oxaliplatin 130 mg/m2 d8 (GemOx). In all three treatment arms, cycles were repeated every 3 wks. Progression-free survival after 3 months was evaluated as a primary end-point. Results: At the interim analysis, 44, 45, and 46 pts had been included into the respective treatment arms. Median age was 63 yrs (range 40–74), 92% of pts presented with a KPS >70%, and 76% had metastatic disease. Stratification was performed with regard to KPS and stage of disease, and pts were accordingly well balanced between treatment groups. At the time of evaluation, 263 treatment cycles were evaluable for toxicity. Generally, hematotoxicity was low with regard to grade 3–4 anemia, leukopenia, and thrombopenia: 0%, 0%, 0% for CapOx, 18%, 0%, 0% for CapGem, and 0%, 5%, 15% for GemOx. Alopecia grade <2 occurred in 18%, 25%, and 32% of pts. Palmar-plantar erythrodysesthesia grade ≥ 2 was observed in 5% of patients each in the CapGem and the CapOx arm. Conclusion: At present time, all three treatment regimens CapOx, CapGem, and GemOx are comparably well tolerated and show a low profile of side effects. A comparative analysis of treatment efficacy will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann La-Roche Roche Germany
Prevention of chemotherapy induced alopecia with scalp hypothermia: An evaluation of the Penguin Cold Cap system
Authors: S. M. Wills, A. Ravipati, M. Nguyen, I. A. Jaiyesimi, J. Margolis, D. Zakalik, D. Decker
Journal: Journal of Clinical Oncology (2008)

20716 Background: Methods of scalp cooling previously tested to prevent chemotherapy induced alopecia (CIA) have had variable efficacy. We present data from a pilot study of the Penguin Cold Cap system (PCC) (Medical Specialties of California) used to minimize CIA in breast cancer patients receiving a chemotherapy regimen with a combination of doxorubicin (A), cyclophosphamide (C), or taxane (T). Methods: Patients with a diagnosis of stage I-IIIC breast cancer, receiving a chemotherapy regimen containing A-C or T were recruited. The first 2 caps are placed 20 minutes each prior to infusion to begin scalp cooling process. Caps are changed every 30 minutes to maintain cooled scalp temperature throughout chemotherapy and for 3 hours after. Patients were given instructions on hair care and are followed during and 24 weeks post treatment. Grading was based on the World Health Organization and Dean’s grading scale for alopecia. Success was defined as no need for cosmetic devices (i.e. wig) due to CIA. Results: Of the 17 patients originally enrolled, 1 patient had metastatic disease and was withdrawn due to the possibility of scalp metastasis, 6 patients opted out of the study after cycle 1 due to time of treatment or beginning hair loss and 1 patient was removed from study for non-compliance. Of the 9 remaining patients, 5 were receiving a regimen containing AC, 2 received TAC, 1 received AC-T and 1 received CT. Four of the AC patients 4 had grade 2 alopecia 3 weeks post chemotherapy and 1 patient had grade 3–4 alopecia discontinuing treatment after cycle 2. TAC patients both had grade 3–4 alopecia after cycle 1. One patient received AC-T and had grade 2–3 alopecia after cycle 8, and 1 patient received CT with grade 2 alopecia after cycle 4. Conclusions: All patients experienced some hair loss above the ear on each side of the head, however it was minimal. The hair loss that was experienced for most patients was uniform and not patchy. Although the results of the preservation were variable, most patients who completed treatment (66%) had no need for a cosmetic device and the treatment was well tolerated. We found in this small study, the PCC system was most effective for treatment regimens containing AC; CT and somewhat effective in AC-T, however the PCC does not seem to be as effective in TAC. No significant financial relationships to disclose.
Increased Expression Of NGF In Hepatocytes Is An Early Event In Iron Overloaded Mouse By Transcriptome Analysis
Authors: Masayo Yamamoto, Hiroki Tanaka, Lynda Addo, Satoshi Ito, Motohiro Shindo, Katsuya Ikuta, Katsunori Sasaki, Takaaki Ohtake, Mikihiro Fujiya, Yoshihiro Torimoto, Yutaka Kohgo
Journal: Blood (2013)
Cancer-specific T cell receptor isolation for cancer immunotherapy
Authors: Debbie Emma Baker, Linda Hibbert, Luise Weigand, Samantha Paston, Ruth Ryan, Zoe Donnellan, Ruth Simmons, Kathy Hale, Louise Conlon, Joseph Dukes, Vanessa Clark, Caroline Boudousquie, Giovanna Bossi, Emma Hickman, Alex Powlesland, Annelise Vuidepot, Namir Hassan, Bent Jakobsen
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Malignant cells may be recognised by T cells binding cell surface Class I HLA (Human Leukocyte Antigen)-peptide complexes presenting disease-associated epitopes. Many cancer patients have been shown to generate CD8 cytotoxic T cell responses to tumour-associated antigens. However
High Efficiency Molecular Delivery with Sequential Low-Energy Sonoporation Bursts
Authors: Kang-Ho Song, Alexander C. Fan, John T. Brlansky, Tammy Trudeau, Arthur Gutierrez-Hartmann, Michael L. Calvisi, Mark A. Borden
Journal: Theranostics (2015)

Microbubbles interact with ultrasound to induce transient microscopic pores in the cellular plasma membrane in a highly localized thermo-mechanical process called sonoporation. Theranostic applications of in vitro sonoporation include molecular delivery (e.g., transfection, drug loading and cell labeling), as well as molecular extraction for measuring intracellular biomarkers, such as proteins and mRNA. Prior research focusing mainly on the effects of acoustic forcing with polydisperse microbubbles has identified a "soft limit" of sonoporation efficiency at 50% when including dead and lysed cells. We show here that this limit can be exceeded with the judicious use of monodisperse microbubbles driven by a physiotherapy device (1.0 MHz, 2.0 W/cm(2), 10% duty cycle). We first examined the effects of microbubble size and found that small-diameter microbubbles (2 µm) deliver more instantaneous power than larger microbubbles (4 & 6 µm). However, owing to rapid fragmentation and a short half-life (0.7 s for 2 µm; 13.3 s for 6 µm), they also deliver less energy over the sonoporation time. This translates to a higher ratio of FITC-dextran (70 kDa) uptake to cell death/lysis (4:1 for 2 µm; 1:2 for 6 µm) in suspended HeLa cells after a single sonoporation. Sequential sonoporations (up to four) were consequently employed to increase molecular delivery. Peak uptake was found to be 66.1 ± 1.2% (n=3) after two sonoporations when properly accounting for cell lysis (7.0 ± 5.6%) and death (17.9 ± 2.0%), thus overcoming the previously reported soft limit. Substitution of TRITC-dextran (70 kDa) on the second sonoporation confirmed the effects were multiplicative. Overall, this study demonstrates the possibility of utilizing monodisperse small-diameter microbubbles as a means to achieve multiple low-energy sonoporation bursts for efficient in vitro cellular uptake and sequential molecular delivery.
What if it really was an accident? The psychology of unintentional doping
Authors: Derwin King Chung Chan, Nikos Ntoumanis, Daniel F Gucciardi, Robert J Donovan, James A Dimmock, Sarah J Hardcastle, Martin S Hagger
Journal: British Journal of Sports Medicine (2015)

Doping refers to the use of prohibited performance-enhancing substances or methods in sport. It is considered a serious offence in sport that has many negative consequences, including titles being stripped, bans from participating, damage to reputation and ill health. As doping is assumed to be a pre-meditated action, engaging in this behaviour has been predominantly attributed to athletes’ decision-making processes and moral values or obligations.1 An increasing volume of literature has focused on the psychological factors associated with doping or doping intention, such as motivation, sportsmanship, moral disengagement and social-cognitive factors.1

These studies make a central assumption that doping is a consciously controlled and goal-directed behaviour. However athletes may dope unintentionally because they are not aware that food, drinks, supplements, or medications may contain doping substances.2 ,3 Therefore, one of the key antidoping strategies of WADA, apart from doping control, is to enhance athletes’ antidoping awareness and their capacity to avoid unintentional doping.

Unintentional doping could lead to adverse analytical findings (AAFs) in doping controls (eg, …
Phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine (GEMOX) in cancer of unknown primary (CUP)
Authors: G. R. Varadhachary, J. C. Blais, M. N. Raber, R. Lenzi, P. M. Hoff, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2005)

4140 Background: CUP patients (3–5% of all cancers) show response rates with combination chemotherapy ranging from 20–30% with little impact on median survival. We are evaluating GEMOX in this population since the combination shows synergy in preclinical studies, is well tolerated and is active in pancreatic and lung cancer (common primaries in CUP). Methods: Patients with a metastatic CUP diagnosis who were chemo naive or had received one previous therapy were eligible. Women with axillary only nodes were excluded. Results: 16 patients are enrolled in the study so far. All are evaluable for toxicity and 14 patients who have had at least one post-treatment CT scan are evaluable for response. Median age is 56 yrs. 63% of patients have adenocarcinoma, 6% squamous carcinoma and rest have undifferentiated tumors. 93% of patients have an ECOG performance status of 0–1. 4/16 patients (25%) of the patients have 4 or more organs involved in the metastatic process. 11 patients have received GEMOX first line and 5 patients have received GEMOX second line. The overall response rate is 36% with an additional 7% and 29% showing a minor response and stable disease respectively. Median TTP is 10.3 weeks for the combined group. Grade 3–4 hematologic toxicity was seen in 4/16 (25%) patients (3 patients with neutropenia and 1 patient with thrombocytopenia). The only significant non-hematologic toxicity was grade 3 nausea in 4/16 (25%) patients. 10/16 (63%) patients showed grade 1–2 sensory neuropathy. Conclusions: Preliminary data suggest that Gemcitabine-Oxaliplatin is an active and well-tolerated combination in patients with CUP. Additional patients will be accrued. No significant financial relationships to disclose.
Quality of life (QOL) predicts for progression-free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib compared to interferon-alpha (IFN-α)
Authors: D. Cella, J. Z. Li, J. C. Cappelleri, A. Bushmakin, C. Charbonneau, S. T. Kim, I. Chen, M. D. Michaelson, R. J. Motzer
Journal: Journal of Clinical Oncology (2007)

6594 Background: In a recent international, randomized phase III trial, sunitinib malate, an oral multitargeted receptor tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET and FLT3 with both antitumor and antiangiogenic effects, was associated with statistically superior clinical efficacy and superior health-related QOL vs. IFN-a as first-line therapy in patients with mRCC (Motzer et al, Proc ASCO 2006;24:2s [Abstract LBA3]). Here we report a substudy of baseline QOL variables predicting PFS. Methods: 750 mRCC patients were randomized 1:1 to receive either sunitinib 50 mg orally once daily in repeated 6-week cycles (4 weeks on treatment followed by 2 weeks off) or IFN-a (9 MU via subcutaneous injection 3 times weekly). QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index's Disease-Related Symptoms subscale (FKSI-DRS), and the patient self-rated overall health state (EQ-VAS) from the EuroQol Group's EQ-5D self-report questionnaire. For all QOL endpoints, higher scores indicated better outcomes (better QOL or fewer symptoms). Cox proportional-hazards model was used to test which baseline QOL variables predict PFS while controlling for other baseline demographic and clinical factors as well as treatment. Because the three QOL scores are correlated (r=0.61–0.69), three separate univariate models were fitted. Results and Conclusions: All three baseline QOL variables were predictive of PFS: better baseline FACT-G, FKSI-DRS and EQ-VAS scores were associated with longer PFS. When QOL and other baseline variables were controlled in the models, the superior treatment effect of sunitinib on PFS remained robust and large (See the table below). [Table: see text]
The 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: a practical chronicle of progress
Authors: Edmund M.T. Lau, Yuichi Tamura, Michael D. McGoon, Olivier Sitbon
Journal: European Respiratory Journal (2015)

The first World Health Organization (WHO) Symposium on Pulmonary Hypertension was held in 1973 in response to the sudden increase in the number of patients with primary pulmonary hypertension (PPH) [1]. This epidemic was related to the intake of appetite-suppressing drugs and only 17 clinicians and scientists convened at the landmark first WHO meeting. Back then, PPH was a mysterious condition without any known therapy. Two decades later, in 1993, the first consensus guideline on PPH endorsed by a specialist society was published [2]. The chairman of the 1993 consensus document, Lewis Rubin (University of California, San Diego, CA, USA), recognised the limited knowledge and science in the field at the time, and remarked some years later that "our task was relatively easy…since the published literature was fairly limited. Accordingly, our guidelines were largely driven by expert opinion" [3]. Since then, we have witnessed dramatic leaps in our knowledge of both the basic and clinical science of pulmonary hypertension. Intravenous epoprostenol, the first of many targeted pulmonary arterial hypertension (PAH) therapies that are currently available, gained US Food and Drug Administration approval in 1995. The turn of the 21st century saw the emergence of efficacious oral therapies that have altered the care of patients with PAH. For the busy clinician, what is new in the 2015 ESC/ERS guidelines on pulmonary hypertension? <http://ow.ly/QwKUx>
Abstract 3738: Body mass, weight, and body size and uterine leiomyoma in the Korea Nurses’ Health Study
Authors: Jung Eun Lee, Ji Eun Lee, Eunyoung Cho, Hee Jung Jang, Heeja Jung, Hea-Young Lee, Su Kim, Ok Soo Kim
Journal: Cancer Research (2015)

Abstract Background: Body mass and body size may influence uterine leiomyoma development in Asian populations. Methods: We examined the associations of body mass index, weight change, and childhood, adolescent or current body size with history of uterine leiomyoma in the Korea Nurses’ Health Study. History of uterine leiomyoma and anthropometric factors were assessed through self-administered questionnaires. We included only women who had experienced pregnancies to avoid detection bias. As a result, a total of 5670 women were included and 560 women reported that they had uterine leiomyoma. The median age of women was 38 years. We calculated odds ratios(OR)s and 95% confidence interval (95% CI)s adjusted for potential risk factors for uterine leiomyoma. Results: Current body mass index was associated with higher odds of having uterine leiomyomas; multivariate OR (95% CI) was 1.52(1.03-2.25; P for trend = 0.003) comparing ≥27.5 with 18.5-23 kg/m2. Body size in adulthood was associated with increased odds of having uterine leiomyomas (P for trend = 0.002), whereas childhood or adolescent body size was not. Also, women with greater change in body weight since the first year of college tended to have higher odds of having uterine leiomyomas, compared to those whose weight had been stable. Conclusion: We found that body mass and weight gain in adulthood were associated with increased odds of having uterine leiomyoma in Korean women, but body mass in early life was not. Citation Format: Jung Eun Lee, Ji Eun Lee, Eunyoung Cho, Hee Jung Jang, Heeja Jung, Hea-Young Lee, Su Kim, Ok Soo Kim. Body mass, weight, and body size and uterine leiomyoma in the Korea Nurses’ Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3738. doi:10.1158/1538-7445.AM2015-3738
A mouse GITRl fusion protein drives T cell activation and antitumor activity in preclinical mouse models of cancer
Authors: Rebecca Leyland, Amanda Watkins, Lisa Bamber, Natalie Tigue, Lesley Young, Michelle Morrow, Scott Hammond, Robert Wilkinson, Ross Stewart
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts GITR is a member of the TNFR superfamily of proteins and is expressed on resting regulatory T cells and on other T cells, and NK cells, following activation. Signals through GITR have been shown to drive increased T cell activity and reduced regulatory T cell function. In order to
Abstract 15938: Mice With XX Chromosomes Develop More Severe Hypoxia-Induced Pulmonary Hypertension Than With XY Chromosomes Regardless of Their Gonadal Sex
Authors: Soban Umar, Alex Centala, Andrea Iorga, Salil Sharma, Arthur P Arnold, Mansoureh Eghbali
Journal: Circulation (2014)

Rationale: Female rodents have shown protection against development of experimental pulmonary hypertension (PH). Estrogen has been shown to be protective against experimental PH. The precise role of sex hormones and sex chromosomes in this protection is still not clearly understood. The four core genotypes (FCG) model comprises mice in which sex chromosome complement (XX vs. XY) is independent of animal’s gonadal sex. The four genotypes are XX gonadal males or females, and XY gonadal males or females. As females have demonstrated protection against development of experimental PH, we hypothesized that having an extra X chromosome may render protection against the development of PH. Methods: Inbred C57BL/6 four core genotype mice were gonadectomized at day 75 after birth to eliminate the role of gonadal hormones in adulthood, and 30 days after gonadectomy, were placed in hypoxia chamber (10% oxygen) for three weeks (n=4-5 per group). Direct cardiac catheterization was performed terminally to assess cardiopu...
The Risk of Alcohol Intake in Men and Women
Authors: Steven Schenker, K. Vincent Speeg
Journal: New England Journal of Medicine (1990)

The concentration of alcohol in the blood and other tissues is the result of its intake route, usually oral, its distribution, and its rate of elimination. Although the enzymes primarily responsible for alcohol metabolism, the alcohol dehydrogenases, are present in many tissues, the liver has traditionally been considered the principal site of alcohol metabolism. In this issue of the Journal, Frezza et al.1 report that alcohol dehydrogenase in the gastric mucosa may contribute substantially to alcohol metabolism, that this effect varies with sex, and that the gastric metabolism of alcohol is decreased in women and men with chronic alcoholism. . . .
CXCR5+CD8+ T cells are localized in B cell follicles and germinal centers and exhibit regulatory and anti-tumor function
Authors: Fuliang Chu, Sattva S Neelapu
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Germinal centers (GC) are specialized anatomic sites where B cells undergo somatic hypermutation, clonal expansion, and affinity-based selection. Stringent regulation of GC reactions is critical for homeostatic B cell development, as well as T-dependent humoral immunity against
Multicenter Implementation of a Treatment Bundle for Patients with Sepsis and Intermediate Lactate Values
Authors: Vincent X. Liu, John W. Morehouse, Gregory P. Marelich, Jay Soule, Thomas Russell, Melinda Skeath, Carmen Adams, Gabriel J. Escobar, Alan Whippy
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Treatments for patients with sepsis with intermediate lactate values (≥2 and <4 mmol/L) are poorly defined.To evaluate multicenter implementation of a treatment bundle (including timed intervals for antibiotics, repeat lactate testing, and intravenous fluids) for hemodynamically stable patients with sepsis and intermediate lactate values in the emergency department.We evaluated patients in annual intervals before and after bundle implementation in March 2013. We evaluated bundle compliance and compared outcome measures across groups with multivariable logistic regression. Because of their perceived risk for iatrogenic fluid overload, we also evaluated patients with a history of heart failure and/or chronic kidney disease.We identified 18,122 patients with sepsis and intermediate lactate values, including 36.1% treated after implementation. Full bundle compliance increased from 32.2% in 2011 to 44.9% after bundle implementation (P < 0.01). Hospital mortality was 8.8% in 2011, 9.3% in 2012, and 7.9% in 2013 (P = 0.02). Treatment after bundle implementation was associated with an adjusted hospital mortality odds ratio of 0.81 (95% confidence interval, 0.66-0.99; P = 0.04). Decreased hospital mortality was observed primarily in patients with a heart failure and/or kidney disease history (P < 0.01) compared with patients without this history (P > 0.40). This corresponded to notable changes in the volume of fluid resuscitation in patients with heart failure and/or kidney disease after implementation.Multicenter implementation of a treatment bundle for patients with sepsis and intermediate lactate values improved bundle compliance and was associated with decreased hospital mortality. These decreases were mediated by improved mortality and increased fluid administration among patients with a history of heart failure and/or chronic kidney disease.
The Occupational Health of De-Miners in Afghanistan
Authors: Michael Peel
Journal: Journal of the Royal Society of Medicine (1995)

In the last few years there has been increasing awareness of the problems of landmines. This has focused on the ethics of landmine use, and the dangers to the local population of minefields. It has culminated in a much needed campaign for a moratorium on landmine manufacture. There are, however, millions of mines left in almost all parts of the world, which can create an indefinite hazard. The only solution is the slow and painstaking task of clearing these minefields. The health and safety of de-miners has not been previously discussed in any detail. This paper addresses the hazards to the people clearing minefields, with specific reference to the activities of the HALO trust in Afghanistan. De-miners are subject to the same hazards from mines as the general population, but put themselves at additional risk by entering minefields deliberately. These hazards can be controlled by a safe system of work and the appropriate use of personal protective equipment.