tbuckley/cabot-search huggingface dataset:
Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial
Authors: Scott P. Kelly, Barry I. Graubard, Gabriella Andreotti, Naji Younes, Sean D. Cleary, Michael B. Cook
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Evidence suggests that obesity in adulthood is associated with increased risk of "clinically significant" prostate cancer. However, studies of body mass index (BMI) across the adult life course and prostate cancer risks remain limited. Methods: In a prospective cohort of 69 873 men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined associations of prediagnostic BMI across the adult life course with risk of incident prostate cancer and fatal prostate cancer (prostate cancer–specific mortality). At 13 years of follow-up, we identified 7822 incident prostate cancer cases, of which 3078 were aggressive and 255 fatal. BMI trajectories were determined using latent-class trajectory modeling. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: BMI at age 20 years, 50 years, and baseline questionnaire (mean age = 63 years) were associated with increased risks of fatal prostate cancer (HRs = 1.27–1.32 per five-unit increase). In five BMI trajectories identified, fatal prostate cancer risk was increased in men who had a normal BMI (HR = 1.95, 95% CI = 1.21 to 3.12) or who were overweight (HR = 2.65, 95% CI = 1.35 to 5.18) at age 20 years and developed obesity by baseline compared with men who maintained a normal BMI. Aggressive and nonaggressive prostate cancer were not associated with BMI, and modest inverse associations were seen for total prostate cancer. Conclusions: Our results suggest that BMI trajectories during adulthood that result in obesity lead to an elevated risk of fatal prostate cancer.
The Effects of Hydroxyurea on the Thrombin Generation and Microparticles in Sickle Cell Anemia Patients
Authors: Patrick Van Dreden, Grigoris T Gerotziafas, Barry J Woodhams, Mourad Chaari, Robert Girot, Amir Kartechi, Vassiliki Galea, Francois Lionnet, Ismail Elalamy
Journal: Blood (2011)
Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer
Authors: M. Nakabayashi, W. Xie, M. M. Regan, D. M. Jackman, P. W. Kantoff, W. K. Oh
Journal: Journal of Clinical Oncology (2006)

4646 Background: High dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low dose ketoconazole (LDK). Relatively little is known about the efficacy of LDK in AIPC. We evaluated the efficacy of LDK and of subsequent dose escalation from LDK to HDK as secondary hormonal therapy in patients with AIPC. Methods: We retrospectively identified patients with AIPC in a single institution treated with LDK (200 mg PO TID) as secondary hormonal therapy with or without concomitant steroids. Additionally, patients were identified who received dose escalation to HDK (400 mg PO TID) after experiencing a rising prostate-specific antigen (PSA). Results: 138 patients were eligible for the study. Median age was 64 years (range: 41–84); median PSA at initiation of ketoconazole was 37.4 ng/ml (range: 0.8–2279). Patients received LDK as either second (25.4%), third (50.0%) or fourth (21.7%) line hormonal therapy. Thirty-nine of 138 patients (28.3%, 95% CI 20.9%–36.6%) treated with LDK treatment experienced PSA declines ≥50%. Median duration of LDK was 6.4 months in responders and 2.9 months in non-responders. Dose escalation to HDK subsequently was performed in 55 (40%) patients, seven of whom (12.7%) demonstrated a subsequent PSA decline ≥50% (5 LDK responders and 2 LDK non-responders, respectively). Overall time to progression with LDK with or without dose escalation was 3.5 months (range 0.1 + –61 months). The most common reversible adverse effect on LDK was grade 1 or 2 fatigue (12.3%). 41.8% of dose escalation group experienced either aggravation or development of toxicities. The most common toxicities on HDK were nausea (16.4%) and fatigue (14.5%). Conclusions: LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, and appears to be less toxic. Few patients responded to the dose escalation from LDK to HDK but durable additional responses occurred in some. No significant financial relationships to disclose.
GW26-e2181 Association of LPA genetic polymorphisms with coronary artery disease in the Xinjiang Han and Uygur population of China
Authors: Chunlan Dong, Zhenyan Fu, Bei Wang, Qing Zhu, Erdenbat Cha, Ding Huang, Fen Liu, Huayin Li, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
Mixed Fields on RHD Typing As an Indicator of Malignancy-Associated Loss of Heterozygosity on Chromosome 1p in Myeloid Neoplasm
Authors: Signy Chow, Jacob M Pendergrast, Gorka Ochoa-Garay, Vikas Gupta, Muhammad Ejaz Munir, Cuihong Wei, Kenneth J Craddock, Suzanne Kamel-Reid, Christine Cserti-Gazdewich
Journal: Blood (2014)
Prognostic factors of localized extremity rhabdomyosarcomas: The results of a pooled analysis from U.S. and European cooperative groups.
Authors: O. Oberlin, A. Rey, K. L. Brown, G. Bisogno, E. Koscielniak, M. Stevens, D. S. Hawkins, W. H. Meyer, T. H. La, J. R. Anderson
Journal: Journal of Clinical Oncology (2010)

9505 Background: We present pooled data from 643 patients (pts) treated in 14 studies conducted by European and American cooperative groups. Methods: Clinical factors, including age, histology, site of primary (hand and foot vs others), size, invasiveness (T), nodal involvement (N) and post surgical group (complete R0, microscopic residue R1 or macroscopic residue / biopsy only R2), chemotherapy (CT) type and duration, radiation therapy (RT) and period of treatment (before or after 1995) were looked at for their impact on survival (OS). Results: The 5 and 10 year OS are 67% (se 1.8) and 62% (se 2) respectively. By univariate analysis, OS is adversely influenced by age > 3 years, size > 5 cm, T2 stage, N1 stage, cooperative group (Europe vs US), incomplete initial surgery and treatment before 1995. Site and alveolar histology are less significant. RT has no impact. Many of these variables are associated. Pts treated by the US group were more often operated on and had more complete surgery at diagnosis than pts treated in Europe. In multivariate analysis OS is strongly correlated to age, T stage, N stage, initial surgery, treatment period and cooperative group. The better survival rate of tumors treated by the US group is observed for grossly resected tumors (R0 or R1) only. OS survival is 86% (se 3) for US pts as compared to 68% (se 4) for European pts (p=0.004). When considering the R0 and R1 tumors separately (n=252) by univariate analysis, OS is significantly influenced by the completeness of initial surgery (R0 vs R1, p=0.05), T stage (p=0.02), and site of the tumour (p=0.02). Longer CT duration (> 27 weeks) is associated with a better OS (p=0.002). RT had no impact. In multivariate analysis, if CT duration is not considered, cooperative group (p=0.001), site (p=0.001) and T stage (p=0.05) are significant. Completeness of initial surgery has no impact. However, adding duration of chemotherapy to the model, site of the primary remains significant (p=0.006) but T status and cooperative group are no longer significant. Conclusions: This analysis confirms the role of many prognostic factors, but in grossly resected tumors it identifies that the duration of chemotherapy has an important impact. No significant financial relationships to disclose.
Immunophenotype and Immunoglobulin Variable Genes (IgVH) Mutation Status in Chronic Lymphocytic Leukemia (CLL). New Prognostic Patterns Detection and Target Therapy.
Authors: Raul Gabus, Otto Pritsch, Ana I. Landoni, Sergio Bianchi, Cecilia Canessa, Adriana Tiscornia, Gabriel Borelli, Faride Uturbey, Juan Enrique Bodega
Journal: Blood (2006)
The Strategy of Early Nilotinib Switch Based on Failure to Achieve Optimal Molecular Targets on Imatinib May Not Overcome the Negative Impact of a Low OCT-1 Activity in De-Novo CP-CML Patients
Authors: Deborah L. White, Verity A Saunders, Amity Frede, Kelvin GrootObbink, Cassandra Slader, David T. Yeung, Michael Osborn, Anthony K. Mills, Andrew Grigg, Timothy P Hughes
Journal: Blood (2011)
Doctor in Germany sent to prison for raping and sexually assaulting patients and coworkers
Authors: Ned Stafford
Journal: BMJ (2016)

A leading vascular surgeon in Germany who heavily sedated patients and coworkers whom he then raped, sexually assaulted, and photographed was today sentenced to seven years and nine months in prison and banned from practising medicine for five years. 

The surgeon, a former chief doctor at Bamberg Hospital in northern Bavaria, has maintained his innocence since his arrest in 2014. He said that medical examinations and photographs were for research. The prosecutor had asked for a sentence of …
Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms
Authors: Ana Babic, Ying Bao, Zhi Rong Qian, Chen Yuan, Edward L. Giovannucci, Hugues Aschard, Peter Kraft, Laufey T. Amundadottir, Rachael Stolzenberg-Solomon, Vicente Morales-Oyarvide, Kimmie Ng, Meir J. Stampfer, Shuji Ogino, Julie E. Buring, Howard D. Sesso, John Michael Gaziano, Nader Rifai, Michael N. Pollak, Matthew L. Anderson, Barbara B. Cochrane, Juhua Luo, JoAnn E. Manson, Charles S. Fuchs, Brian M. Wolpin
Journal: Cancer Research (2016)

Abstract Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case–control study of 470 cases and 1,094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging SNPs in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7 ng/mL; P &amp;lt; 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [95% confidence interval (CI), 1.27–7.16; Ptrend = 0.02] compared with men in the bottom quintile. Among women, circulating leptin was not associated with pancreatic cancer risk (Ptrend = 0.21). Results were similar across cohorts (Pheterogeneity = 0.88 for two male cohorts and 0.35 for three female cohorts). In genetic analyses, rs10493380 in LEPR was associated with increased pancreatic cancer risk among women, with an OR per minor allele of 1.54 (95% CI, 1.18–2.02; multiple hypothesis-corrected P = 0.03). No SNPs were significantly associated with risk in men. In conclusion, higher prediagnostic levels of plasma leptin were associated with an elevated risk of pancreatic cancer among men, but not among women. Cancer Res; 76(24); 7160–7. ©2016 AACR.
An unusual cause of colonic stricture with polyps
Authors: Shuhei Fukunaga, Hidetoshi Takedatsu, Hiroko Muta, Keiichi Mitsuyama, Takuji Torimura
Journal: Gut (2016)

A 70-year-old man with no history of IBD was admitted to our department with right-sided abdominal pain and bloating. He was a non-smoker and a non-alcoholic drinker. Vital signs on initial examination were within normal range. Abdominal examination revealed a palpable tender mass (5×5 cm) in the right abdomen. Laboratory results were as follows: white cell count, 13.4×109/L; haemoglobin, 13.5 g/dL; platelet count, 311×109/L; erythrocyte sedimentation rate, 64 mm/hour; albumin, 3.62 g/dL; and C-reactive protein, 3.97 mg/dL.

Abdominal CT revealed a thickening of the wall (localised high-density mass-forming lesion) in the ascending colon (figure 1A). …
Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals
Authors: Yaling Wu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, Haijiao Zhao, Peihao Chen, Xiangbing Qi, Eric Erquan Zhang
Journal: Cell Metabolism (2016)
Induction chemotherapy (IC) with docetaxel/cisplatin/5-fluorouracil (TPF) followed by cisplatin-containing concomitant chemoradiotherapy (CRT) in fit patients with locally advanced head and neck cancer (LAHNC): The CONDOR study—A study of the Dutch Head and Neck Society.
Authors: Chantal Driessen, J. P. De Boer, Hans Gelderblom, Coen R.N. Rasch, Martin de Jong, Berit M Verbist, Margot Et Tesselaar, Winette T.A. Van Der Graaf, J. H. Kaanders, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2013)

6057 Background: Standard treatment for patients (pts) with LAHNC is concomitant CRT containing cisplatin. In general 70% of the pts receive all planned cisplatin cycles. TPF IC is associated with survival benefit, but has never been studied in combination with standard CRT. We aimed to determine if TPF followed by cisplatin-containing CRT, in 2 different schedules, was feasible. Methods: In this multicenter randomized phase II trial LAHNC pts, PS 0-1, were treated with maximal 4 TPF courses (T 75 mg/m 2 , P 75mg/m 2 and F 750 mg/m 2 day 1-5) and thereafter randomized between P 100 mg/m 2 on days 1, 22, 43 combined with conventional RT (arm A) or P 40 mg/m 2 weekly, maximally 6, combined with accelerated RT (arm B). Primary endpoint was feasibility, defined as receiving ≥ 90% of the planned total radiation dose. Based on power analysis 70 pts were needed. Results: Following an interim-analysis, the study was early terminated after inclusion of 65 pts because only 32% of pts could be treated with the full cisplatin dose during CRT after TPF. 81,5% of pts was male, median age was 56 yrs and PS was 0 in 79% and 1 in 21%, primary site: oral cavity (23%), oropharynx (57%), hypopharynx (12%), larynx (8%). 3 pts did not start TPF; 6/62 pts were not randomized after TPF, due to death (1), toxicity (3) or severe PD (2). RR after TPF was CR 4%, PR 64% and SD 28% in the randomized pts. 27 pts were randomized in arm A and 29 in arm B. 97% of the pts received at least 90% of the planned total radiation dose. However, in arm A only 6 of the 27 pts (22%) and in arm B 12 of the 29 pts (41%) received the total planned chemotherapy part of the CRT. Most common grade 3-4 toxicity during TPF was febrile neutropenia (18%),and during CRT arm A vs arm B dehydration (26% vs 14% ), dysphagia (26% vs 24%), mucositis (22% vs 57%) and creatinin increase (19% vs 3%). After a median follow-up of 21 (7-42) months 66% of the pts was still alive. Conclusions: After TPF IC cisplatin-containing concomitant CRT is not feasible in LAHNC, because the total planned dose of cisplatin could only be administered in 32% of the pts due to severe toxicity. Clinical trial information: NCT00774319.
Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery
Authors: Raquel Requejo-Aguilar, Ana Alastrue-Agudo, Marta Cases-Villar, Eric Lopez-Mocholi, Richard England, María J. Vicent, Victoria Moreno-Manzano
Journal: Biomaterials (2016)
Weekly topotecan-gemcitabine for pretreated small cell lung cancer (SCLC) patients (pts): A phase II study.
Authors: M. Domine, J. L. Gonzalez-Larriba, J. Lopez-Vilariño, R. Alfonso, A. Leon, J. Puente, V. Casado-Echarren, L. Rodriguez, G. Rubio, F. Lobo
Journal: Journal of Clinical Oncology (2010)

e18070 Background: Topotecan IV at dose of 1.5 mg/m2 days 1 –5 every 3 weeks is the standard treatment for pretreated SCLC pts. Weekly topotecan at dose of 4 mg/m2 has shown an excellent toxicity profile. Based in previous studies of our group using gemcitabine doublets in pretreated SCLC pts, we conducted a prospective phase II study to determine the activity of this combination in this population. Methods: Pts were eligible if they had measurable or evaluable disease, previous treatment with platins, adequate hepatic, renal and bone marrow function. Topotecan dose was 4 mg/m2 IV days 1 and 8, and gemcitabine 1,250 mg/m2 (30-minute IV infusion) days 1 and 8 every 3 weeks. Results: 58 pts were enrolled, 54 male and 4 female. Median age was 61 years (range 39- 83); 92% had PS 0 or 1; 38 pts had sensitive disease and 20 pts had refractory disease. The median of cycles per patient was 3 (range 1-3). All the pts were evaluable for efficacy and toxicity. In an intent to treat analysis the response rate was 12% (95% CI: 5%-23%), 1 patient with sensitive disease achieved a complete response (1.7%). 21% of pts showed stable disease and 67% progression. Median time to progression was3 months (95% CI: 2-4 m) and median survival 5 months (95% C.I: 3-7 m). Toxicity was very mild with grade 3-4 hematological toxicity in 17% of patients, without non-hematological grade 3-4 toxicity. 2 patients developed skin toxicity grade 1-2. Conclusions: Weekly topotecan- gemcitabine does not seem to improve the efficacy of the standard schedule of IV topotecan in monotherapy. The tolerability is acceptable. In our opinion further development of this combination is not warranted. No significant financial relationships to disclose.
Prediction of chemo-response in serous ovarian cancer
Authors: Jesus Gonzalez Bosquet, Andreea M. Newtson, Rebecca K. Chung, Kristina W. Thiel, Timothy Ginader, Michael J. Goodheart, Kimberly K. Leslie, Brian J. Smith
Journal: Molecular Cancer (2016)

Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA. We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets. The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets. These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.
Randomized open-label phase 2 study of MM-111 and paclitaxel (PTX) with trastuzumab (TRAS) in patients with HER2-expressing carcinomas of the distal esophagus, gastroesophageal (GE) junction, and stomach who have failed front-line metastatic or locally advanced therapy.
Authors: Crystal Shereen Denlinger, Sun Jin Sym, Johanna C. Bendell, Maria Alsina, David Watkins, Yee Chao, Antonio Cubillo, Pamela L. Kunz, Weijing Sun, Lene Baeksgaard, Li-Tzong Chen, Kerry Horgan, Sasha Frye, Arthur J. Kudla, Charlotte Fenton McDonagh, Akos Gabor Czibere, Victor M. Moyo, Benoist Chibaudel, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2014)

TPS4148 Background: HER2 overexpression occurs in ≤ 20% of GE cancers, and front-line fluoropyrimidine/platinum with TRAS increases survival in HER2+ GE junction/gastric cancer patients. Weekly PTX has activity after front-line therapy in GE cancers. HER3 is overexpressed in < 87% of GE cancers and expression is associated with poor prognosis. HER3 is activated by its ligand, heregulin, to form a potent signaling heterodimer with HER2 and is emerging as a key tumorigenic node and mediator of drug resistance. MM-111 is a novel molecule that inhibits heregulin-activated HER3 signaling in HER2+ tumors. In preclinical gastric cancer models, MM-111 potentiates the antitumor activity of TRAS and PTX, and also mitigates HER3-mediated resistance. MM-111 has been combined with PTX and TRAS in a multi-arm, dose escalation phase 1 trial. Most common dose-limiting toxicities include myelosuppression, GI toxicities, and electrolyte abnormalities. Methods: This is a randomized open-label multi-center Phase 2 study of PTX and TRAS +/- MM-111 in patients with HER2 expressing advanced GE adenocarcinoma. Arms are stratified for prior TRAS exposure, geographic region, and ECOG performance status. Patients are dosed with PTX at 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle; TRAS at 4 mg/kg loading dose then 2 mg/kg/weekly and MM-111 at 20 mg/kg/weekly. Pretreatment tumor biopsies and archived tumor tissue will be collected to explore the correlation of biomarkers associated with HER2, HER3 and heregulin signaling activity (1) between archived and pretreatment samples and (2) with clinical response. The primary objective is progression-free survival. Secondary objectives are overall survival, time to treatment failure, objective response rate, duration of response, safety, and health-related quality of life. Pharmacokinetic and immunogenicity analysis of MM-111 will be performed. Enrollment is ongoing. Clinical trial information: NCT01774851.