tbuckley/cabot-search huggingface dataset:
Individualized Tamoxifen Dose Escalation: Confirmation of Feasibility, Question of Utility
Authors: Daniel L. Hertz, James M. Rae
Journal: Clinical Cancer Research (2016)

Tamoxifen may require metabolic activation to endoxifen for efficacy in treating hormone receptor-positive breast cancer. Dose escalation in patients with low endoxifen concentrations could enhance treatment efficacy. This approach is clinically feasible, and successfully increases endoxifen concentrations; however, it is unknown whether patients benefit from individualized tamoxifen dose escalation. Clin Cancer Res; 22(13); 3121-3. ©2016 AACRSee related article by Fox et al., p. 3164.
Burkitt Tumor: Tissue Culture, Cytogenetic and Virus Studies
Authors: Sarah E. Stewart, Elizabeth Lovelace, Jacqueline J. Whang, V. Anomah Ngu
Journal: JNCI Journal of the National Cancer Institute (1965)

Tumor cells that retained their original histology were grown from a biopsy taken from a 7-year-ofd male with a Burkitt tumor. The cells grew in suspension, usually in clumps varying from a few to hundreds of cells in a free-floating mass. This cell line was designated SL1. A herpes-like virus, which caused some cell degeneration of the tumor cells in culture, was observed by electron microscopy. Supernatant fluids from the SL1 cultures failed to produce a cytopathogenic effect in inoculated cell lines. A specific chromosome alteration was observed in the cells from the original tumor and in the cultured tumor cells.
How submarine and guided missile technology can help reduce injury and improve performance in cricket fast bowlers
Authors: Dean J McNamara, Tim J Gabbett, Geraldine Naughton, John W Orchard
Journal: British Journal of Sports Medicine (2016)

There are three formats of cricket competition (multiday unlimited overs with approximately 150–300 overs delivered by one team, 50-over and Twenty20; T20—20 overs). An over is a measure of workload—6 consecutive deliveries by a bowler. A delivery carries the ball to the batsman 20 m away at speeds varying from 80 to 160 km/h.

In these three forms of cricket, a bowler's workload may vary from 60 to 4 overs in one of the matches. Because of this varying workload and intensity, cricket match-play provides a complex challenge for clinicians and coaches.1 Arguably, no other professional sport has experienced greater changes in competitive workload demands than cricket over the past 10 years; perhaps most specifically via the introduction of T20 cricket.

Fast bowlers are at greater risk of injury than their team mates,2 and the nature of the injuries sustained tend to involve extensive rehabilitation periods. These injuries are largely associated with repetitive large forces experienced by fast bowlers during their bowling actions resulting in accumulated stresses.3 With a predominance of …
Predicting response to amitriptyline in posttraumatic stress disorder
Authors: J R Davidson, H S Kudler, W B Saunders, L Erickson, R D Smith, R M Stein, S Lipper, E B Hammett, S L Mahorney, J O Cavenar
Journal: American Journal of Psychiatry (1993)

This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD).Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale.Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD.The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.
Variations in Diabetes Prevalence in Low-, Middle-, and High-Income Countries: Results From the Prospective Urban and Rural Epidemiological Study
Authors: Gilles R. Dagenais, Hertzel C. Gerstein, Xiaohe Zhang, Matthew McQueen, Scott Lear, Patricio Lopez-Jaramillo, Viswanathan Mohan, Prem Mony, Rajeev Gupta, V. Raman Kutty, Rajesh Kumar, Omar Rahman, Khalid Yusoff, Katarzyna Zatonska, Aytekin Oguz, Annika Rosengren, Roya Kelishadi, Afzalhussein Yusufali, Rafael Diaz, Alvaro Avezum, Fernando Lanas, Annamarie Kruger, Nasheeta Peer, Jephat Chifamba, Romaina Iqbal, Noorhassim Ismail, Bai Xiulin, Liu Jiankang, Deng Wenqing, Yue Gejie, Sumathy Rangarajan, Koon Teo, Salim Yusuf
Journal: Diabetes Care (2016)

The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors.The prevalence of diabetes, defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses.Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28-1.31]), male sex (1.19 [1.13-1.25]), urban residency (1.24 [1.11-1.38]), low versus high education level (1.10 [1.02-1.19]), low versus high physical activity (1.28 [1.20-1.38]), family history of diabetes (3.15 [3.00-3.31]), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33-3.96]), and BMI (≥35 vs. <25 kg/m(2); 2.76 [2.52-3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%).Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.
New Agents in Chronic Myelogenous Leukemia
Authors: Jorge Cortes, Francis Giles
Journal: Journal of the National Comprehensive Cancer Network (2003)

Multiple new agents are currently being developed in chronic myelogenous leukemia (CML). Most of these agents are now being investigated in patients who have developed resistance to imatinib. Their mechanisms of action are diverse and many may be synergistic with imatinib. These agents will be used soon in different combinations, most likely including imatinib, with the hope of obtaining a complete blockade of the intracellular pathways that are triggered by Bcr-Abl. If this is successful, complete eradication of disease may become a reality for the majority of patients with CML.
GENO-07A MECHANISM OF MUTANT TERT PROMOTER ACTIVATION SHARED ACROSS CANCER TYPES
Authors: Robert Bell, H. Tomas Rube, Alex Kreig, Andrew Mancini, Shaun Fouse, Raman Nagarajan, Serah Choi, Chibo Hong, Daniel He, Melike Pekmezci, John Wiencke, Margaret Wrensch, Susan Chang, Kyle Walsh, Sua Myong, Jun Song, Joseph Costello
Journal: Neuro-Oncology (2015)

The human telomerase is an enzyme critical for maintaining telomere length and chromosomal stability in stem cells. The transcriptional regulation of the telomerase reverse transcriptase (TERT) gene, encoding the catalytic subunit of telomerase, is a rate-limiting step in modulating telomerase activity. Although normally silenced in somatic cells, TERT is aberrantly expressed in 90% of aggressive cancers, highlighting this event as a hallmark of tumorigenesis. Reactivating telomerase helps cells with finite lifespan to achieve limitless proliferative potential and bypass cellular senescence induced by DNA replication-associated telomere shortening. Recently discovered non-coding mutations in the TERT promoter are among the most common genetic alterations observed across multiple cancer types. Specifically, one of two positions, G228A or G250A, is mutated in 20% of medulloblastomas, 44% of hepatocellular carcinomas (HCC), 66% of urothelial carcinomas of the bladder, 71% of melanomas, 78% of oligodendrogliomas, and 83% of primary glioblastomas (GBM). The common mutation sites may create de-novo ETS family transcription factor binding sites, but the precise mechanism of how these mutations confer increased TERT expression has remained elusive. Here, a focused siRNA screen of the many ETS transcription factors expressed in GBM identifies GABPA as the single ETS factor to selectively regulate the mutant but not the wild type TERT promoter. Single molecule binding assays and ChIP-qPCR analysis reveal that GABPA is exclusively recruited to the mutant allele in vitro and in vivo respectively. Furthermore, this allelic recruitment is consistent across four tested cancer types, highlighting a shared mechanism underlying mutant TERT promoter activation. Tandem flanking native ETS motifs critically cooperate with these mutations to activate TERT, likely by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression across multiple cancers.
The Addition of Bevacizumab to Erlotinib for Malignant Pleural Effusion: a Case Report with Pharmacokinetic Analysis
Authors: Satoru Miura, Hiroshi Kagamu, Chiyo Imamura, Rie Kondo, Masaaki Okajima, Satoshi Watanabe, Junta Tanaka, Ichiei Narita, Yusuke Tanigawara, Hirohisa Yoshizawa
Journal: Annals of Oncology (2014)
Efficacy and safety of irinotecan-based chemotherapy in poor risk patients suffering from metastatic colorectal cancer
Authors: A. Deptala, M. Magon, J. Omyla-Staszewska, A. Asendrych, M. Paluszewska
Journal: Journal of Clinical Oncology (2007)

14581 Background: Irinotecan (CPT11) combination chemotherapy has provided a significant advancement in the management of patients with metastatic colorectal cancer (MCRC). However, there was some data indicating that poor risk cases might not benefit from longer survival with CPT11-based chemotherapy, mainly due to higher regimen toxicity. Purpose: To evaluate the hypothesis, whether CPT-11- based chemotherapy can produce similar TTP and OS in a group of poor risk MCRC patients in comparison to standard risk MCRC cases. Patients and Methods: Out of 170 CRC patients treated in our departments between 2002 - 2006, 36 poor risk MCRC patients (poor risk group was defined as 2 or more criteria being fulfilled, i.e. PS &gt;1, and/or elevated serum LDH, and/or &gt;1 metastatic site, and/or prior adjuvant chemotherapy), were chosen for this analysis and compared retrospectively with our standard risk MCRC cases. The poor risk arm consisted of 9 females and 27 males, in age between 40–76 [median 63,5]. All the patients were treated with CPT11-based chemotherapy, according to either AIO or de Gramont regimen. Results: In the analyzed poor risk group the confirmed RR (CR+PR) after six months of the treatment was 25,0% what was much lower than in standard risk group (RR = 40%), however did not reach the statistical significance; additional 52,8% of patients achieved SD; 8 patients (22,2%) progressed during therapy. The median TTP was 9 months and the median OS was 15 months, what were not statistically different from the standard risk group; 2-year survival obtained 27,8% of patients. No grade (G) 4 toxicity was observed. The most common adverse events (AE) were diarrhea [25% - 9 pts] and neutropenia [11.1% - 4 pts], but G3 AE were noted only in 2 and 1 person respectively. Conclusions: This analysis showed, that CPT11-based chemotherapy is an effective and safe treatment option even for poor risk patients suffering from MCRC. Although the RR was lower in comparison to standard risk cases it did not translate into shorter TTP as well as OS. Similar to ours results were published in various scientific papers. To define a precise role of various optimization strategies of CPT11-based chemotherapy in MCRC, randomized prospective multicenter studies are mandatory. No significant financial relationships to disclose.
Nondisclosure of Complementary and Alternative Medicine Use to Primary Care Physicians
Authors: Judy Jou, Pamela Jo Johnson
Journal: JAMA Internal Medicine (2016)

Dima M. Qato, PharmD, MPH, PhD; Jocelyn Wilder, MPH; L. Philip Schumm, MA; Victoria Gillet, BS; G. Caleb Alexander, MD, MS
Abstract 15557: Comorbid Illness Profiles Predict Greater Length of Stay for Women: an Analysis of 93,242 Heart Failure Admissions
Authors: Christopher S Lee, Quin E Denfeld, Julie T Bidwell, Ruth Masterson Creber, Jill M Gelow, James O Mudd, Harleah G Buck
Journal: Circulation (2012)

Introduction: There is significant heterogeneity in length-of-stay (LOS) associated with hospitalizations for heart failure (HF). We hypothesized that comorbid illness profiles identified among women admitted for HF would be predictive of significant differences in LOS and explain some of this heterogeneity. Methods: We analyzed all adult female hospitalizations for HF (primary diagnosis) from the 2009 Agency for Healthcare Research and Quality (AHRQ) National Inpatient Sample (n=93,242). Latent class mixture modeling was used to identify distinct profiles among 32 complementary AHRQ and Deyo-Charlson comorbidity measures, and profiles were labeled according to dominant characteristics. Negative binomial regression was used to quantify differences in inpatient LOS by profile adjusting for age, race, payer, weekend admission, and regional income, as well as hospital size, control, urban/rural location, and teaching status. Results: Four distinct comorbid illness profiles were identified (model entropy = 0....
Entrapment of doxorubicin or mitoxantrone into liposomal paclitaxel for combination chemotherapy
Authors: Gopal Anyarambhatla, Zafeer Ahmad, Sushil Prem, Imran Ahmad
Journal: Cancer Research (2004)

643  Simultaneous delivery of two or more cytotoxic agents in chemotherapy treatment for cancer is relatively a new approach that holds great promise. Liposomal delivery system is one of the promising avenues for such a delivery due to its unique ability to entrap both hydrophilic and hydrophobic molecules. In addition, the size and charge of liposomes can be controlled to optimize drug loading and tumor uptake. We were able to package two anti-cancer drugs, namely paclitaxel and doxorubicin (DOX) or paclitaxel and mitoxantrone (MTO) in a single liposomal delivery system using proprietary NeoLipid™ technology. First, liposomal paclitaxel (LEP-ETU) was prepared at 2mg/mL drug concentration. Subsequently, DOX or MTO was entrapped into LEP-ETU at various drug to lipid ratios. The entrapment efficiency studies suggest that the process limits for DOX or MTO concentrations in LEP-ETU were 1.5mg/mL or 2.2mg/mL respectively. Entrapping an additional drug like MTO or DOX had no effect on the particle size up to five days after reconstitution indicating the absence of aggregation. Paclitaxel content remained intact even after entrapping an additional drug like MTO or DOX, suggesting that it can co-exist with another drug in a single delivery system without compromising the particle size and entrapment efficiency. It is possible that by using the liposome drug delivery carrier, one could effectively deliver a multitude of entrapped drugs to tumor cells with concomitant decrease in their toxicity to healthy cells. Pre-clinical studies using these novel formulations are planned.
THU0561 Salivary IL-1 Alpha and IL-1 Beta Levels Associated with Oral Mucosal Disease Activity in Behcet's Disease: Table 1.
Authors: N. Alpay-Kanıtez, B. Toz, F. Berktaş, M. Güzel, S. Ergun, M. Koray, N. Polat, B. Erer, A. Gül
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Recurrent oral aphthous ulcers are the common manifestation of the Behçet9s disease, and they are indistinguishable from ulcers of recurrent aphthous stomatitis (RAS). There is no reliable biomarker reflecting disease activity in BD, and systemic acute phase reactants are not helpful in evaluation of active disease, especially in patients with predominantly mucocutaneous activity. <h3>Objectives</h3> We aimed to assess the potential of salivary interleukin-1 alpha and beta (IL-1A and IL-1B) concentrations as well as two S100 proteins, namely S100A12 (calprotectin) and S100A13 in comparison to their serum levels in BD, RAS, and healthy controls. <h3>Methods</h3> A total of 67 patients with BD, 43 patients with RAS, and 22 healthy controls with no history of aphthous ulcers or other oral mucosal disorders (NA) comprised the study group. BD patients fulfilled the ISG criteria for the diagnosis, and patients with active systemic disease were excluded. Patients with BD and RAS were classified as active and inactive according to the presence or absence of aphthous ulcers at the time of sample collection. Unstimulated saliva and serum samples were collected after overnight fasting. IL-1A, IL-1B, S100A13 and calprotectin levels were measured by ELISA, and concomitant measurements of ESR and serum CRP levels of BD patients were recorded. <h3>Results</h3> At the time of sample collection, 38 BD patients (18 male, mean age: 39,1±10,3) were classified as active and 29 patients (18 male, mean age: 38,9±10,5) as inactive. Similarly, 19 patients with RAS (11 male, mean age: 36,6±8,7) were active and 24 patients (7 male, mean age: 36,7±10,1) were inactive state. Mean values of salivary and serum ELISA measurements are given in Table 1. Salivary IL-1A and IL-1B levels were higher in BD patients compared to RAS and NA even during inactive state (IL-1A p&lt;0.001 for RAS and p&lt;0.001 for NA, IL-1B p&lt;0.001 for RAS and p=0.003 for NA). There was a correlation between IL-1A and IL-1B levels, but IL-1A increase was more prominent in active BD patients. No correlation was detected between salivary IL-1A and S100A13 levels. Serum CRP and ESR were within normal range in BD patients, and they showed no correlation with salivary measurements. <h3>Conclusions</h3> These results reveal a role for IL-1A and IL-1B in the development of oral aphthous ulcers, and increased salivary IL-1A levels without an increase in S100A13 levels may suggest pyroptosis or other causes of cellular damage as its source. Further studies are necessary both to improve saliva collection and analysis methods and to search the biomarker potential of salivary IL-1A and IL-1B concentrations in the management of mucocutaneous and systemic manifestations of BD. <h3>Acknowledgements</h3> There is no conflict of interest. <h3>Disclosure of Interest</h3> None declared
Enhanced Host Resistance to Transplantable Murine Lymphosarcoma in Swiss Mice by Combined Immunostimulation With BCG and Polyinosinic-Polycytidylic Acid2
Authors: T. B. Poduval, M. Seshadri, K. Sundaram
Journal: JNCI Journal of the National Cancer Institute (1984)

Combined immunostimulation with BCG and double-stranded polyinosinic-polycytidylic acid (poly I . poly C) was more effective than single-modality immunostimulation in suppressing tumor growth in inbred Swiss mice. BCG sensitization followed by administration of poly I . poly C on the day of tumor cell injection significantly prolonged the survival period against parental lymphosarcoma (LS) and its ascites variant (LS-A). BCG and poly I . poly C given together on the day of tumor cell injection suppressed only LS-A and not LS. BCG or poly I . poly C given alone did not result in tumor cures. Silica injection given 2 days before poly I . poly C injection completely abrogated the antitumor effect of sequential treatment with BCG and poly I . poly C. Silica treatment given on and beyond the day of poly I . poly C injection did not abrogate the antitumor effect. This observation indicated that intact macrophage effector function was essential at the time of tumor cell inoculation to obtain an effective antitumor action.
Identification of a predictive signature based on immunohistochemical (IHC), RNA-seq and epigenetic profiling of melanoma metastases for response to ipilimumab-based immunotherapy.
Authors: Teofila Seremet, Alexander Koch, Sofie Wilgenhof, Max Schreuer, Yanina Jansen, Danielle Lienard, Veronique Del Marmol, Kris Thielemans, Nicolas Van Baren, Pierre Coulie, Tim De Meyer, Wim Van Criekinge, Bart Neyns
Journal: Journal of Clinical Oncology (2015)

9052 Background: Ipilimumab (Ipi) improves the survival of patients (pts) with advanced melanoma. Combination of Ipi with an autologous monocyte-derived DC therapy (TriMixDC-MEL) may further improve patient outcome (Neyns et al., 2014 ASCO AM). A predictive melanoma tissue signature for the clinical efficacy of Ipi and TriMixDC is needed to optimize individualized treatment strategies. Methods: Between 01/2011 and 05/2013 freshly frozen melanoma metastases were collected from pts treated with Ipi (n: 9), TriMixDC-MEL (n: 2), or TriMixDC-MEL plus Ipi (n: 14). Samples were profiled by IHC (incl. CD3, CD8, PanMel, MCSP, CD20, CD163, DC-LAMP, Casp-3, Ki-67, PHH3, HLA class I, vWF), RNA-seq and MBD-seq (genome-wide DNA methylation profiling). Tumor response was assessed according to the irRC. Results: Five pts obtained a complete response (CR), 6 obtained a mixed response (MR), and there was no evidence of tumor response in 14 pts (NR). A total of 26 metastases (15 obtained prior to and 11 post therapy) were profiled by IHC and 18 were additionally profiled by RNA and MBD-seq. Intra-tumor CD3 and CD8 T cell infiltration was observed in 23/26 samples, with variable pattern and extent of infiltration. None of the 3 pts with absent CD3/CD8 infiltration in their tumor core regions responded to Ipi-based immunotherapy. The differential analysis of the RNA-seq data resulted in a list of 195 genes with a statistically significant difference in expression between CR and NR (false discovery rate < 0.05). A gene ontology enrichment analysis revealed that the differentially expressed genes were enriched for immune-related ontologies. The MR expression profiles clustered together with the NR group. MBD-seq revealed differences in methylation status between CR and NR pts. These differences in methylation status were not linked to the observed differences in RNA expression. Conclusions: Comprehensive analysis of melanoma metastases with gene expression and methylation status provides a distinct profile that identifies long-term responders to Ipi-based immunotherapy. Prospective validation is warranted.