tbuckley/cabot-search huggingface dataset:
Sorafenib and sunitinib in renal cell cancer: A study based on register data.
Authors: A. E. Ambring, U. K. Stierner, A. S. Oden, I. N. Bjorholt
Journal: Journal of Clinical Oncology (2011)

4600 Background: There is limited data on the use of sorafenib (SO) and sunitinib (SU) in clinical practice in the treatment of advanced renal cell cancer (RCC). It has been suggested that the sequence by which the drugs are given is important for the outcome. Register data could add valuable real-life evidence to previous clinical trial data on these drugs. Methods: Sweden has a long tradition of keeping registers, e.g. Swedish Cancer Registry since 1958, Cause of Death Register 1961 and Register on Prescribed Pharmaceuticals (RPP) 2005. All Swedish citizens have a unique personal identification number and retrospective studies can be conducted by linking information from several registers. Individuals with RCC and prescribed SO and/or SU were extracted from the RPP. The date of first purchase was captured from the RPP and duration of treatment was studied. Analysis was carried out on the actual observed data on duration of treatment for first-line/mono therapy. For sequential therapy time on treatment and time to death were analyzed without making the assumption that patients (pts) survived first-line therapy, i.e. the risk to stop or to die during first-line/monotherapy was accounted for. Results: We found 123 pts starting with SO and 261 pts with SU. Median time on therapy was 148 days for SO and 138 for SU. Forty-three of these pts were treated with SO+SU and 54 with SU+SO in sequence. The influence of the duration of the first-line therapy on the risk of discontinuing second-line treatment was significantly different for SO compared to SU (p=0.0096). For death a corresponding difference was assessed (p=0.0278). Small differences were seen for the calculated median duration, 252 vs 234 days for combined endpoint and 398 vs 347 days for death (excluding time between treatments) but for the proportions of pts remaining without endpoint at 1.5 years larger differences were seen. All differences were in favor of those starting with SO. Conclusions: In clinical practice in Sweden treatment duration of SO and SU is similar when given as first-line treatment or monotherapy. The order in which treatment is given in sequential therapy is important and the results indicate that SO as first-line treatment is a favorable choice.
Modelling the in-utero initation of ETV6-RUNX1 in childhood acute lymphoblastic leukaemia using human pluripotent stem cells
Authors: Simon Richardson, Charlotta Böiers, Alya Zriwil, Virginia Turati, John Brown, Dapeng Wang, Javier Herrero, Andrew Smith, Sten Erik Jacobsen, Tariq Enver
Journal: The Lancet (2016)
Evaluation of axillary node dissection on measures of upper-extremity disability and overall quality of life after breast cancer surgery.
Authors: S. A. McLaughlin, A. S. Parker, N. N. Diehl, M. Arnold, J. H. Nguyen, E. A. Perez
Journal: Journal of Clinical Oncology (2010)

9063 Background: Axillary lymph node dissection (ALND) can increase the risk of upper extremity disability after breast cancer surgery, but there has been little effort to evaluate if this translates to a negative effect on overall quality of life (QoL). Motivated by this, we compare baseline and six-month QoL and upper extremity disability measures between women undergoing ALND or sentinel node biopsy (SLNB). Methods: We prospectively identified 92 women with T1-3 breast cancer undergoing surgery with either SLNB (n=52) or ALND (n=40) between 12/08 and 12/09. A single surgeon (SAM) performed all surgeries. Patients completed the FACT-B (higher score = better QoL) and Disabilities of Arm, Shoulder and Hand (DASH; higher score = more disability) questionnaires prior to surgery and at six months postoperatively. We abstracted demographic and clinical covariates from our ongoing Axillary Surgery Registry database. Results: SLNB and ALND patients were similar in regard to age (p=0.84), marital status (p=0.44), ethnicity (p=0.2), BMI at baseline (p=0.68), and BMI at six months (p=0.59). Women undergoing ALND had a larger median tumor size (2.8cm vs 1.6cm, p<0.001) and were more likely to receive chemotherapy ± radiation therapy (p<0.006). At baseline, the two groups reported similar median FACT-B QoL scores (ALND=117 vs. SLNB=114; p=0.7) while the ALND group reported slightly higher DASH disability (ALND=7.1 vs. SLNB=2.6; p=0.09). At six months, the median FACT-B QoL scores remained similar between the two groups (ALND=114 vs. SLNB=117, p=0.51) despite the fact that the difference in DASH disability scores strengthened (ALND 12.5 vs. SLNB 5.8, p=0.046). Interestingly, the median change in scores from baseline to six months was similar for the two groups on both the FACT-B (ALND= 0.5 vs. SLNB= −1.0, p=0.54) and DASH (ALND= −4.2 vs. SLNB= −2.5, p=0.96). Conclusions: The need for independent validation notwithstanding, our data suggest that increases in upper extremity disability associated with ALND do not translate to a significant effect on disease specific QoL at six months. Continued follow up is necessary to determine if and when QoL outcomes diverge between ALND and SLNB patients. No significant financial relationships to disclose.
Use of pharmacogenomics in predicting bleomycin-induced pulmonary toxicity in testicular cancer patients
Authors: J. Nuver, M. Van Zweeden, M. Lutke Holzik, C. Meijer, H. Hoekstra, A. Suurmeijer, R. Hofstra, H. Groen, D. Sleijfer, J. Gietema
Journal: Journal of Clinical Oncology (2004)

4531
Toxic Effect of Dimethylnitrosamine in Cows
Authors: Nils Koppang
Journal: JNCI Journal of the National Cancer Institute (1974)

Cattle were exposed to both commercial dimethylnitrosamine (DMNA) and herring meal in which DMNA developed during processing and storage. DMNA levels in fish meal were titrated by bioassay and compared with those obtained by analytic chemistry. Accumulation of OMNA started when the dosage exceeded a threshold value of 0.1 mg DMNA/kg body weight. Signs of liver damage became apparent when the dosage was 12-26 mg DMNA/kg. If DMNA was removed from the diet, recovery from the liver damage occurred. Regeneration of liver tissue and neoformation of hepatic veins to replace those lost by obliteration were established. The vessel wall damage extended beyond the liver. The hepatic vein branches especially showed necrosis of the endothelium, edema, and bleeding in the vessel wall itself with subsequent narrowing of the lumen. These veno-occlusive changes caused increased fibrosis of the liver. Tumors were not observed in cattle exposed to DMNA.
Phase II trial of belotecan in patients with sensitive relapsed small-cell lung cancer after irinotecan-containing chemotherapy
Authors: J. Jeong, B. Cho, H. Choi, S. Shin, Y. Lee, S. Kim, J. Sohn, J. Kim
Journal: Journal of Clinical Oncology (2008)

8118 Background: Belotecan (CKD 602) is a novel camptothecin analogue, topoisomerase-I inhibitor. This phase II trial was conducted to evaluate the activity of belotecan against irinotecan-sensitive relapsed small-cell lung cancer (SCLC). Methods: A sensitive relapsed SCLC patients, who were defined as relapsed at least 3 months after having achieved complete or partial response to 1st line irinotecan-containing chemotherapy, were eligible for this trial. Belotecan was administered as a 30-minute daily intravenous injection at a dose of 0.5mg/m2/day for 5 consecutive days every 3 weeks. From the second cycle, the daily dose of belotecan was adjusted to one of three dose levels, 0.4, 0.5, or 0.6 mg/m2/day, based on the toxicities after the each cycle. The primary endpoint was response rate. The group sequential design of Chang et al. was utilized and the estimated sample size was 50 patients (stage I - 20 patients; stage 2 - 15 patients; stage 3 - 15 patients). The study has a 80% power to detect a response rate of 15%, with an alpha error 5%. Results: Between March 2006 and May 20007, a total of 20 patients were enrolled (median age 64, 16M/4F, ECOG PS 0–1 95%). A total of 96 cycles of belotecan were delivered with a median of 6 cycles. The dose level of belotecan was 0.4 mg/m2/ day in 23 cycles, 0.5 in 56, and 0.6 in 17. The most frequent grade 3/4 toxicities were related to myelosuppression including neutropenia in 95% of patients and thrombocytopenia in 45%. No febrile neutropenia or bleeding was observed. Nonhematol- ogic toxicities were mild. There was no treatment- related death. Overall objective response rates were 25% (95% CI, 4.2 - 45.8; 0 CR, 5 PR, 10 SD, 5 PD). With a median follow-up duration of 8.0 months, median time to progression was 4.7 months (95% CI, 3.9 - 5.5) and median overall survival wasn’t reached. Conclusions: Belotecan shows promising activity in relapsed SCLC, with predictable and manageable toxicities. Therefore, this topoisomerase-I inhibitor is a treatment option for patients with sensitive relapsed SCLC, who have responded to irinotecan-containing chemotherapy. No significant financial relationships to disclose.
Should all adult cystic fibrosis patients with repeated nontuberculous mycobacteria cultures receive specific treatment? A 10-year case–control study
Authors: Christiane Albrecht, Felix Ringshausen, Sebastian Ott, Dirk Wagner, Jessica Rademacher, Michael Schneider, Tobias Welte, Mathias W. Pletz
Journal: European Respiratory Journal (2016)

The disease caused by nontuberculous mycobacteria (NTM) forms a broad clinical spectrum from asymptomatic infection to fatal disseminated disease in humans. While many NTM patients have underlying pulmonary diseases, NTM symptoms are undifferentiated from symptoms of patients with chronic pulmonary structural diseases [1]. Not all CF patients with MAC detected in respiratory samples require anti-mycobacterial treatment <http://ow.ly/X66gt>
Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor antagonist
Authors: Q Sun, JM Woodcock, A Rapoport, FC Stomski, EI Korpelainen, CJ Bagley, GJ Goodall, WB Smith, JR Gamble, MA Vadas, AF Lopez
Journal: Blood (1996)
The British Clinical Staging of Breast Cancer
Authors: M. Harmer
Journal: BMJ (1958)

The need to classify cases of cancer of the breast has long been recognized.Probably the first staging, which took into account the patient's age, the extent of the disease, and the histology, as well as lactation or preg- nancy, was that of Lee and Stubenbord (1928).This was adjudged to be too unwieldy, and the staging which gained most acceptance was that of Portmann (1937,
Dose escalation by HDR brachytherapy using free-hand needle application without template in localized prostate cancer
Authors: R.-P. Mueller, M. Bendel, M. Kocher, U. Engelmann
Journal: Journal of Clinical Oncology (2005)

4715 Purpose/Objective: To report on biochemical outcome in pts with loc. Prostate cancer (LPC) treated with HDR-brachytherapy(HDR-BT) + 50,4 Gy 3D conformal external radiotherapy (3D-EBRT). Materials/Methods: From 07/1999 to 06/2004, 137 pts with LPC were treated with 3D-EBRT (50,4 Gy to the small pelvis) followed by 2(-3) x HDR-BT. HDR-BT was performed between 2 and 3 weeks after 3D-EBRT by placing needles fan-like in a free-hand technique without using a template to optimize dose coverage. HDR doses were calculated to be 8 Gy to the target for each fraction (2 (-3) fx). Total biologically effective doses(BED) to the prostate was between 75 - 95 Gy. Acute and late toxicities were scored acc. to the EORTC/RTOG morbidity grading scales. Results: All pts completed treatment. 86 pts, who were treated until 12/2002, could be compl. evaluated in respect to overall survival, PSA relapse free survival and toxicity. The median follow-up was 30 month. By using free-hand needle application, tumor volumes of up to 130 ml could be treated with a high level of conformity (COIN) without having any anatomical restrictions. The 5-year actuarial overall-survival for all pts 93%. The 5-year actuarial PSA relapse-free survival rates for low, intermediate and high risk group pts were 100%, 44% and 41% resp. Pts reaching a PSA-nadir below 0.5 ng/ml showed significant better PSA relapse-free survival (52% vs. 22%). Patients with an initial PSA > 20 ng/ml after pelvine lymphnode sampling revealing no metastases, also showed a significant better PSA relapse-free survival (67% vs. 40%). Five patients (5.8%) dev. grade 3 GU toxicities. None had more than grade 2 rectal complications. Conclusion: Our data demonstrate the successful feasibility of HDR-BT + 3D-EBRT as a safe method for escalating the dose to the prostate without increasing risk of acute and late toxicities. Using the free-hand needle application technique offers the possibility of treating even large tumor volumes to high radiation doses and good conformity without having any limitation by the anatomy of the patient. Reaching a PSA-nadir below 0.5 ng/ml or having pelvine lymphnode sampling by an initial PSA > 20 ng/ml showed a significant better PSA relapse- free survival. No significant financial relationships to disclose.
French Brain Tumor Data Bank (FBTDB): Main results on 23,648 cases.
Authors: V. Rigau, H. Mathieu-Daude, D. Figarella-Branger, B. Tretarre, F. Bauchet, M. Fabbro, R. Attaoua, O. L. Chinot, H. Duffau, L. Bauchet
Journal: Journal of Clinical Oncology (2010)

e12536 Background: The objectives of the FBTDB are to create a national histologic registry and a network in order to perform epidemiologic studies, to implement a new database, to perform clinical and basic research protocols, and to harmonize the healthcare of patients affected by primary central nervous system tumor (PCNST). Methods: The French societies involved in Neuro-Oncology (Société Française de Neuropathologie, Association des Neuro-Oncologues d'Expression Française, Société Française de Neurochirurgie) have recently created the FBTDB. For each patients with histologically confirmed PCNST, the neurosurgeon and the neuropathologist fulfill an easy data file containing socio-demographic, clinical, radiologic and anatomopathologic information. Results: In 5 years, 23,648 cases of newly diagnosed PCNST have been recorded. Histologic diagnoses included glioma 47.8%, all other neuroepithelial tumors 4.8%, meningioma 29.3%, neurinoma 7.6%, lymphoma 3.1% and others 7.4%. Cryopreservation was reported for 6,035 PCNST specimens. Clinical and radiologic aspects were also recorded. Tumor resections (R) were performed in 75.5%, while biopsies (B) accounted for 24.5%. Median age (MA), sex, percentage R/B, preoperative Karnofsky performance status (KPS) and number of cryopreserved tumor, will be detailed, for each histology, to the presentation (for example, on 5556 glioblastomas [MA 63 years, male 59.6%, median KPS 83, R 59%, B 41%, 1621 were cryopreserved], on 35 atypical teratoid/rhabdoid tumors [MA 2 years, male 57%, R 90%, B 10%, 18 were cryopreserved]). Conclusions: The interests of such a database are numerous: 1) To observe the number of each type of newly diagnosed and histologically confirmed PCNST in different geographical units. 2) To promote the implementation of epidemiologic studies and to look for the factors influencing the appearance of PCNST. 3) To build a clinical, radiologic and histologic database dedicated to PCNST; making it the largest virtual tumor bank ever for PCNST and therefore carrying out many specific fundamental research and clinical studies. 4) To conduct many specific retrospective or prospective studies concerning rare tumors. No significant financial relationships to disclose.
Pulmonary Carcinoma (Jaagsiekte) of Sheep: Pathologic Findings and Comparison in Multiple-Case and Case-Free Herds
Authors: I. Hod, A. Zimber, U. Klopfer, A.W. Helder, T.A. Nobel, K. Perk
Journal: JNCI Journal of the National Cancer Institute (1974)

During a 2-year intensive study of 3 herds of sheep, alveolar cell carcinoma (lung carcinoma, pulmonary adenomatosis, jaagsiekte) occurred in only 1 herd. This herd also had the highest incidence of various other diseases, such as verminous pneumonia, lung abscesses, chronic interstitial pneumonia, and mediastinal lymphadenitis due to Corinobacterium ovis. Hyper-7S immunoglobulinemia as defined by ultracentrifugal and immunoelectrophoretic analyses was used to indicate diseased animals. In the highly diseased herd, 46 of 550 animals were “hyperimmune.” Postmortem examination of 16 diseased animals revealed 9 jaagsiekte cases and 7 other diseases. The other 2 herds each with 350 animals were “case free.” Virus-like particles, similar to the murine C-type virions, were observed in the primary tumor tissue.
Everything Old Is New Again: Using Nelfinavir to Radiosensitize Rectal Cancer
Authors: Raymond E. Meyn, Sunil Krishnan, Heath D. Skinner
Journal: Clinical Cancer Research (2016)

Abstract Repurposing agents approved for other indications to radiosensitize tumors may be advantageous. The study by Hill and colleagues utilizes nelfinavir, an HIV protease inhibitor (PI), in combination with radiotherapy in rectal cancer in a prospective study. This combination may improve tumor perfusion and regression compared with radiotherapy alone. Clin Cancer Res; 22(8); 1834–6. ©2016 AACR. See related article by Hill et al., p. 1922
Molecular differences between normal breast epithelia, pure DCIS, and DCIS adjacent to invasion.
Authors: Marina Guvakova
Journal: Journal of Clinical Oncology (2012)

50 Background: With the use of screening mammography, the diagnosis of breast ductal carcinoma in situ (DCIS) is increasing worldwide. Currently there are no applied molecular markers to aid in predicting risk of DCIS progression to invasive breast cancer (IBC). Studies predicted that the transition from DCIS to invasive disease was associated with quantitative rather than qualitative differences in gene and protein expression. Methods: We developed monochrome imaging-based method to measure protein expression as a continuous variable in fixed tissue (Furstenau et al. BREA 2010). The insulin-like growth factor I receptor (IGF-IR), Ras oncogene –like protein 1 (Rap1), and a Rho GTPase guanine nucleotide exchange factor Vav2 implicated in the regulation of invasion in preclinical models have been chosen for protein analysis in tissue. In pilot study, we performed quantitative protein profiling on 90 samples of the breast: 17 histologically normal tissues, 16 benign lesions; 15 CIS, and 42 IBC. In addition, we analyzed 24 DCIS: 12 pure and 12 associated with IBC. Results: The expression of the IGF-IR and Rap1 was increased in pure CIS; significantly (P ≤ 0.001) increased in CIS adjacent to IBC as well as in IBC compared with non-cancerous tissue. In the majority of pure DCIS the levels of Vav2 were similar to that in normal epithelia; however, the Vav2 levels were significantly (P&lt;0.01) higher in DCIS adjacent to invasion and in IBC. Moreover, IGF-IR, Rap1 and Vav2 significantly discriminated invasive from non-invasive tissues, with receiver operating characteristic (ROC) area under curve, AUC=0.8. Interestingly, younger women (&lt; 50 years of age) were more likely to develop IBC with increased expression of the Vav2 protein (OR= 2.05; 95% CI 1.08-3.86). No significant correlation was found between IGF-IR, Rap1 expression levels and patient’s age. Conclusions: We conclude that our assessment of protein expression in breast tissue revealed previously unidentified quantitative differences in the IGF-IR, Rap1, and Vav2 protein expression in breast cancer progression series. These findings open door for studies on molecular-based prediction of individualized risk for developing invasion in early diagnosed DCIS.
Internet-Assisted Parent Training Intervention for Disruptive Behavior in 4-Year-Old Children
Authors: Andre Sourander, Patrick J. McGrath, Terja Ristkari, Charles Cunningham, Jukka Huttunen, Patricia Lingley-Pottie, Susanna Hinkka-Yli-Salomäki, Malin Kinnunen, Jenni Vuorio, Atte Sinokki, Sturla Fossum, Anita Unruh
Journal: JAMA Psychiatry (2016)

There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems.To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment.This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232).The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching.Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization.Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P < .001), internalizing scale (effect size, 0.35; P < .001), and total scores (effect size, 0.37; P < .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P < .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P < .001).The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems.clinicaltrials.gov Identifier: NCT01750996.
Political bias, explanatory depth, and narratives of progress
Authors: Steven Pinker
Journal: Behavioral and Brain Sciences (2015)

Abstract Political bias has indeed been a distorter of psychology, not just in particular research areas but in an aversion to the explanatory depth available from politically fraught fields like evolution. I add two friendly amendments to the target article: (1) The leftist moral narrative may be based on zero-sum competition among identity groups rather than continuous progress; and (2) ideological bias should be dealt with not just via diversity of ideological factions but by minimizing the influence of ideology altogether.