tbuckley/cabot-search huggingface dataset:
Woman with gene for Huntington's disease fails in attempt to sue her father's doctors for failing to alert her
Authors: C. Dyer
Journal: BMJ (2015)

A woman whose father refused to let his doctors tell her that he had Huntington’s disease, and who later found that she had the gene, has been barred from bringing a claim for negligence against the NHS trusts involved with his care. A High Court judge has ruled that her case had no chance of success and has struck it out.

The unnamed woman was pregnant at the time and says that she would have had an abortion had she known that her child might be at risk of the hereditary disease.

Her father was convicted of manslaughter on the grounds of diminished responsibility in 2007 after shooting her mother dead. He …
Phase I dose-escalation study of E6201, a MEK-1 inhibitor, in advanced solid tumors.
Authors: M. J. Borad, C. E. Akerele, R. K. Ramanathan, D. W. Northfelt, L. Reyderman, D. Verbel, K. Feit, D. D. Von Hoff, R. Tibes
Journal: Journal of Clinical Oncology (2010)

2505 Background: E6201 is a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)-1 and MEK kinase-1, with anticancer activity in preclinical models. Methods: This phase I, open-label study evaluated E6201 MTD in advanced solid tumors. Inclusion criteria were ECOG PS ≤1 and adequate bone marrow, renal, and liver function. Sequential cohorts of 3-6 subjects were given E6201 30-min IV infusion on Days 1, 8, and 15 of a 28-day cycle starting at 20 mg/m2 and increasing in 100% increments up to 320 mg/m2 until 2 Grade 2 toxicities or 1 DLT was observed. Doses were then increased by ≤50% up to 720 mg/m2 or until the MTD was determined. Blood samples were collected on days 1 and 15 for PK analysis. PD assessment included evaluation of CTC, serum IL-6 and IL-8 levels, and effects on proliferation and signal transduction pathway in skin and tumor biopsies. Results: 25 subjects (median age 66.6 [range 44-87] yr) received E6201 doses from 20 to 40, 80, 160, 320, and 480 mg/m2. At 480 mg/m2, 2 subjects had DLTs (QTc prolongation [Grade 3] and confusional state [Grade 4]). E6201 was reduced to 400 mg/m2, at which 1 subject had CNS toxicity (dizziness). Therefore, the 320 mg/m2 cohort was expanded to 3 additional subjects (total 6); 1 subject had 1 DLT (Grade 2 QTc prolongation) and Grade 2 CNS toxicities (dizziness, dysarthria, ataxia), confirming 320 mg/m2 as the MTD. Most-frequent AEs across doses were nausea (16%), constipation, dizziness, peripheral edema, and vomiting (all 12%, all Grade 1/2). E6201 was rapidly eliminated (mean t3/4=2.47- 5.60 hr). Exposure to E6201 was dose related and comparable on days 1 and 15. A trend for decreasing IL-6 and IL-8 levels was observed without clear dose dependency or duration of effect. Surrogate tissue (skin) biopsies were not informative. One subject with metastatic ocular melanoma had stable disease (>10 months) (B-Raf wild-type) and another, with B-Raf mutant papillary thyroid cancer, a partial remission. Conclusions: The E6201 MTD of 320 mg/m2 IV once weekly for 3 out of a 4-week cycle was well tolerated in patients with advanced solid tumors. An expansion phase at MTD will continue to assess efficacy and determine the optimal schedule using biomarker-driven endpoints and tumor response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai
Management of chronic myelogenous leukemia using therapeutic drug monitoring of imatinib: the French experience of a centralized laboratory
Authors: F. Mahon, S. Bouchet, G. Etienne, L. Legros, D. Réa, F. Guilhot, F. Huguet, K. Titier, N. Moore, J. Reiffers, M. Molimard
Journal: Journal of Clinical Oncology (2008)

7087 Background: The current gold standard treatment of chronic myelogenous leukemia (CML) is imatinib, a tyrosine kinase inhibitor. We have previously shown the necessity to obtain a trough plasma threshold of 1000 ng/mL for efficient treatment of imatinib. We now routinely perform centralized quantification for patients in France. This has allowed the assessment of imatinib therapeutic monitoring and its use in a real life setting. Methods: A database was created from CML patients containing cytogenetic and molecular statuses, the reason of request (monitoring, insufficient response, non-compliance), dose of imatinib and the associated treatments, as well as possible adverse events. Results: After one year of data collection, we had gathered more than 1000 samples for almost 700 patients (mean age 55 years, F/M sex ratio 0.67) treated by imatinib 400 mg (median) range(100–800mg). For these, the mean concentration was 1020 ng/mL (median: 825 ng/mL) with 60% of low concentrations (< 1000 ng/mL). Plasma concentration increased with dose, although inter-individual variability was large and intra- individual variability was smaller. For plasma concentrations 1000 ng/mL this was 510 mg. For 124 patients having had more than 2 samples, only 28% had initial concentration < 1000 ng/mL (mean concentration of 1st sample: 581 ng/mL. Among the 31 patients who initially had a plasma concentration below 1000 ng/mL that subsequently rose above this threshold, about 50% had their imatinib dose increased; the rest did not have a dose modification. In cases where there was suspicion of a drug-drug interaction, the most frequently combined drugs were proton pump inhibitors, diuretics, allopurinol. The most recurrent adverse effects were digestive, hematological and muscular cramps. Conclusions: Although the studied population had same characteristics generally described for this pathology, there was probably selection bias at the beginning of study: we received first and foremost the patients having an insufficient response, and therefore low plasma concentration. Therapeutic drug monitoring of imatinib appears to be helpful for the management of CML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial
Authors: Jeffrey A Cohen, Douglas L Arnold, Giancarlo Comi, Amit Bar-Or, Sheila Gujrathi, Jeffrey P Hartung, Matt Cravets, Allan Olson, Paul A Frohna, Krzysztof W Selmaj
Journal: The Lancet Neurology (2016)
Cancer screening trial to evaluate the efficacy of FDG-PET in healthy subjects: 2-year results of the Hamamatsu Medical Imaging Center study
Authors: S. Nishizawa, M. Inubushi, H. Okada, F. Ozawa, S. Kojima, S. Teramukai, M. Fukushima
Journal: Journal of Clinical Oncology (2006)

1025 Background: Positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) is increasingly used for cancer screening in Japan. Although it is not rare that cancers at early stages are incidentally found on FDG-PET in usual clinical practice, it is still unknown whether FDG-PET is an effective tool for early detection of cancer and decrease of cancer death. To evaluate the efficacy of FDG-PET in cancer screening, we started a prospective study 2 years ago. Methods: From Aug 26 2003 to July 22 2004, 1197 healthy volunteers aged 35 years or older (46.7±7.7y.o.) participated in our cancer screening trial. They are supposed to undergo screening tests annually for 5 years and will be followed for years. The screening tests included whole-body FDG-PET, chest and abdominal CT, brain and pelvic MRI, tumor markers (CEA, CA19–9, SCC, PSA, CA125), and fecal occult blood test. From July 26 2004 to July 22 2005, 1158 subjects of the 1197 underwent the second screening a year after the first one. We made contact with 39 other subjects who skipped the second screening to check the occurrence of cancers. Results: In the 2-year period, primary cancers occurred in 19 subjects. Fifteen cancers (6 thyroid, 3 breast, 2 prostate, 3 lung, 1 ectopic thymus in thyroid grand) were detected on the first year and one (prostate) on the second year by the screening. Ten of the 16 were at stage I. Three subjects with negative findings at the screening developed gastric lymphoma, gastric cancer and malignant lymphoma of the kidney, respectively, within a year after the screening. FDG-PET was positive in 10 of 15 cancers (6 thyroid, 2 breast, 1 prostate and 1 ectopic thymus) on the first year. No PET positive cancer was found on the second year. Sensitivity of the screening tests as a whole and FDG-PET alone for the first year was 78.9% and 52.6%, respectively. Positive and negative predictive values and specificity of FDG-PET were 11.0% (10/91), 99.2% (1097/1106), and 93.1% (1097/1178), respectively. Conclusions: Cancer screening including FDG-PET showed reasonable accuracy and could detect a wide variety of cancers at early stages. This prospective study will clarify the details of efficacy and suitable interval of FDG-PET in cancer screening. No significant financial relationships to disclose.
Molecular Epidemiological Investigation using PFGE and MSP-PCR Assay of Acinetobacter baumannii isolates from Nosocomial Outbreaks
Authors: T Semedo, M Correia, J Quaresma, LM Lito, JMelo Cristino, MJ Salgado, R Tenreiro, A Duarte
Journal: Clinical Microbiology and Infection (2000)
Reply
Authors: Hugh A. Sampson, Roy Gerth van Wijk, Carsten Bindslev-Jensen, Scott H. Sicherer, Suzanne Teuber, Wesley Burks, Anthoney E. Dubois, Kirsten Beyer, Philippe A. Eigenmann, Jonathan M. Spergel, Thomas Werfel
Journal: Journal of Allergy and Clinical Immunology (2013)
Circulating Interferon in Man After Administration of Exogenous Human Leukocyte Interferon&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: G Emödi, M Just, R Hernandez, H R Hirt
Journal: JNCI Journal of the National Cancer Institute (1975)

Interferon was measured at different intervals after the iv, sc, and im application of exogenous human leukocyte interferon to patients with various virus diseases or neoplasms. Interferon injected iv into patients had a half-life of about 15 minutes in the 1st hour and of about 90 minutes in the next 3 hours. Six hours after iv injection of 30 million U, no serum interferon was detectable. With a continuous iv infusion, a relatively high serum interferon level was reached. By the im administration of 1 million U interferon, a peak level of serum interferon (mean value 107 U/ml serum) occurred after 2 hours and was fairly stable for about 6 hours. Twenty-four hours after im application, a low level of serum interferon was still detectable. Similar results were found after sc interferon injections. In a patient with subacute sclerosing panencephalitis, no interferon was found in the cerebrospinal fluid at the time of the highest serum interferon level and 24 hours after two im interferon injections. Only minimal side reactions resulted from sc and im interferon injections. In one patient, a shock reaction occurred after iv application. For therapeutic trials, about 1 million U exogenous human interferon should be injected twice daily im or sc.
Ondansetron: a new antiemetic for patients receiving cisplatin chemotherapy.
Authors: L H Einhorn, C Nagy, K Werner, A L Finn
Journal: Journal of Clinical Oncology (1990)

GR 38032F (ondansetron) is a selective serotonin subtype-3 receptor antagonist with reported antiemetic efficacy in patients receiving cisplatin. This study evaluated the safety and efficacy of ondansetron in three consecutive nonrandomized groups of patients who were receiving a 4- or 5-day regimen of cisplatin (20 to 40 mg/m2/d) combination chemotherapy. Thirty-six patients were enrolled. Thirty-five patients were assessable for efficacy. All patients received three daily intravenous doses of 0.15 mg/kg of ondansetron. Twenty-four patients had received no prior chemotherapy. Twelve of these received ondansetron every 2 hours and 12 received ondansetron every 6 hours. Twelve additional patients who had received at least one prior course of chemotherapy were administered ondansetron every 6 hours. All patients were monitored for emetic episodes (vomiting or retching), adverse events, and laboratory safety parameters. Ten patients (29%) had no vomiting or retching throughout the entire study period and 18 patients (51%) experienced two or fewer emetic episodes during the entire study period. The greatest antiemetic efficacy was on day 1 when 27 patients (77%) had no emesis. The chemotherapy-naive patients responded better than the nonnaive patients on all study days. Reported adverse events were minor, with the most common possibly drug-related event being headache (14% of patients). No extrapyramidal symptoms were observed. Transient increases in total SGOT, and SGPT were observed in some patients.
Lymphoreticular Tumors in Peru&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: P. Correa, G. T. O'Conor, Oscar Misad, Jose Galvez Brandon, Pedro Albujar
Journal: JNCI Journal of the National Cancer Institute (1973)

Population-based data describing lymphoreticular tumors in metropolitan Lima and the results of pathology reviews of solid lymphomas in Lima and Trujillo are presented. Some of the outstanding differences from other sets of international data are mentioned and discussed, with particular attention being given to Hodgkin's disease.
Baseline and temporal patterns of fatigue predict pathological response in patients treated with preoperative chemoradiation therapy (CRT) for rectal cancer
Authors: M. Delclos, S. Krishnan, T. Mendoza, E. Lin, S. Vadhan-Raj, P. Das, C. Crane, Y. Zhang, C. Cleeland, N. Janjan
Journal: Journal of Clinical Oncology (2007)

14522 Background: We investigated whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathological response, a surrogate for treatment outcome. Methods: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Most patients had T3 tumors (94%) and hemoglobin &gt; 12 (85%). Symptom burden was prospectively assessed prior to (baseline) and weekly during CRT by a patient self-reported questionnaire, the MD Anderson Symptom Inventory (MDASI). Survival probabilities were estimated non-parametrically using Kaplan-Meier’s product limit method. Lowess curves were plotted for symptom burden across time. Logistic regression was used to determine whether symptom burden levels predicted for pathological response. Results: Among 51 patients evaluable for pathological response, 9 patients (18%) achieved pCR, and 26 patients (51%) had TDS. The actuarial rates of local control (LC), disease-free survival (DFS), and overall survival (OS) at 2 years were 93%, 76%, and 98%, respectively. Patients with TDS had lower levels of fatigue at baseline and at completion (week 5) of CRT compared to those without TDS (p = 0.03 for both). A similar trend was not observed for other symptom burden parameters of pain, sleep disturbance, appetite, nausea, or feeling of sadness. Evaluation of the potential effect of symptom burden on pCR, LC, DFS, or OS was not possible because of the low number of events during the 2-year median follow-up. Conclusions: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathological response, as gauged by TDS. Unlike studies that have documented improved quality of life among responders, our study demonstrates the converse, i.e. fatigue, a measure of symptom burden, independently predicted for tumor response. This provocative finding could potentially be used to stratify patients into prognostic groups, influence treatment decisions, and/or modify treatment. An evaluation of changes in cytokine profile during CRT is ongoing to determine the molecular basis of this phenomenon. No significant financial relationships to disclose.
The Real World Effectiveness of Hematopoietic Transplant Among Elderly Individuals With Multiple Myeloma
Authors: Aaron N. Winn, Gunjan L. Shah, Joshua T. Cohen, Pei-Jung Lin, Susan K. Parsons
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Hematopoietic stem cell transplant (HSCT) is the preferred treatment for young patients with multiple myeloma (MM), but for older adults there is limited evidence on its effectiveness from clinical trials.
Phase III randomized multicenter trial of surgical resection, BCNU-impregnated wafers, and irradiation versus surgical resection and irradiation alone for treatment of operable, solitary brain metastasis from systemic cancer
Authors: H. B. Newton, C. Volpi, J. Burkart, M. E. Miner, R. Gahbauer, D. K. Pearl, T. Ryken, R. E. Albright, M. Quigley
Journal: Journal of Clinical Oncology (2006)

11513 Background: Metastatic brain tumors (MBT) are the most frequent complication of systemic cancer. With conventional radiotherapy, survival remains poor, ranging from 24 to 32 weeks. Recent randomized trials suggest that surgical resection and irradiation of solitary MBT can extend survival and improve neurological quality of life. However, the role of chemotherapy remains unclear. A phase I/II trial demonstrated that interstitial chemotherapy with BCNU-impregnated wafers was well tolerated in this cohort, with an extended median survival and infrequent local recurrences. Methods: A randomized, multicenter phase III trial was begun to evaluate the ability of BCNU-impregnated wafers to improve survival and local time to progression in comparison to surgical resection and irradiation alone, with an expected accrual of 170 patients. Eligible patients were adults with systemic cancer of the lung or breast, with a solitary, accessible MBT that did not cross the midline or violate the ventricular system. Results: A total of 22 patients (female - 14; 20 with lung cancer), median age 60 years (range 39–77), were enrolled and randomized before the study was closed due to slow accrual. Each patient had undergone maximal surgical resection of the MBT and radiation therapy (35 Gy); wafers were placed in 12 patients (range 2–8 wafers). The median overall survival for the wafer and non-wafer groups were 35.0 and 47.4 weeks, respectively (log rank test, p = 0.54), with a 6-month survival rate of 67% and 56%, respectively (Fishers exact test, p = 0.67). Wafer placement was well tolerated. Conclusions: In this small cohort limited by slow accrual, the use of BCNU-impregnated wafers did not improve survival over surgical resection and irradiation alone. The wafers were well tolerated and did not adversely impact on quality of life. Although animal studies and phase I/II data are suggestive of activity, a large, multicenter, phase III comparative trial will be necessary to determine the efficacy of BCNU-impregnated wafers in patients with solitary, resectable MBT. [Table: see text]
Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger
Authors: E Deloose, P Janssen, M Lannoo, B Van der Schueren, I Depoortere, J Tack
Journal: Gut (2015)

<h3>Objective</h3> Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. <h3>Design</h3> Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. <h3>Results</h3> Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. <h3>Conclusions</h3> Motilin may be an important regulator involved in the pathogenesis of obesity.
구연 : P2/MS값과 간암의 고주파 열치료 후 재발위험도의 관계
Authors: 곽민선, 이정훈, 윤정환, 정고은, 정은욱, 김보현, 김휘영, 명선정, 김원, 김윤준, 김정룡, 김세형, 이재영, 이정민, 한준구, 정진욱, 이효석
Journal: Clinical and Molecular Hepatology (2009)
Relationship of thymidylate synthase levels to outcome of malignant pleural mesothelioma patients treated with pemetrexed-based chemotherapy
Authors: G. Selvaggi, L. Righi, P. Ceppi, E. Bacillo, A. Billè, S. Pandiscia, F. Ardissone, G. V. Scagliotti, M. Papotti
Journal: Journal of Clinical Oncology (2009)

7508 Background: Pemetrexed has shown activity in malignant pleural mesothelioma (MPM) but scanty data are available on the expression of thymidylate synthase (TS), its most important molecular target. Methods: From a database of 75 non-surgical, chemotherapy-naive MPM patients from our Institution in the period 2004–2008, 50 (male/female: 37/13, median age: 65 years) met the selection criteria i.e. epithelial type, availability of thoracoscopic tissue and outcome data. Pemetrexed was administered as single agent (14/50) or in combination with cisplatin or carboplatin (36/50). Retrospectively TS protein expression levels were evaluated by immunohistochemistry and quantified with H-score method. In addition, mRNA extraction was performed in 23 micro-dissected tissues and TS relative levels quantified by RT-PCR. Survival probability was assessed by Kaplan-Meier method and results compared by log-rank test. Cox multivariate analysis for survival was performed adjusting for clinical-pathological variables. Results: Thirty-two patients had progressive disease and 24 had died at the time of the analysis. Median time to progression (TTP) and median survival time (MST) were 11.6 and 20.9 months, respectively. Median TS H-score value was 90 (5–240). No correlation were found with sex, age, PS, stage and chemotherapy regimen. Patients with high TS H-score (4th quartile) had a significantly shorter MST (13.3 vs 21.1 months, p&lt;0.01) and showed a trend for shorter TTP (8.3 vs 11.9 months, p=0.07). Median TS mRNA level was 1.88 (1–3.7 unit-less ratio) and a significant correlation between mRNA and protein expression (RS=0.67, p&lt;0.0001) was found. Patients with high TS mRNA levels (4th quartile) had significantly shorter TTP (8.7 vs 14.7 months, p=0.019) and MST (11.7 vs 24.7, p=0.018). Multivariate analysis for survival indicated that TS protein levels were an independent prognostic factor (HR=2.17; CI 1.04–4.54; p=0.038). Conclusions: TS (protein and mRNA) levels predict outcome of epithelial MPM patients treated with pemetrexed-based chemotherapy. TS quantification, if confirmed in larger prospective studies, could be used to select those patients more likely to respond to chemotherapy. [Table: see text]