tbuckley/cabot-search huggingface dataset:
A comparison of overall and cause-specific survival among patients with low- and intermediate-risk prostate cancer treated with brachytherapy, external beam radiotherapy, or radical prostatectomy
Authors: J. P. Ciezki, C. A. Reddy, P. A. Kupelian, E. A. Klein, C. Robinson, N. Chehade, K. Angermeier, A. Altman, J. Ulchaker
Journal: Journal of Clinical Oncology (2007)

5126 Background: The factors thought to influence overall survival (OS) and cause-specific survival (CSS) in patients treated for low and intermediate-risk prostate cancer (CaP) with brachytherapy (PI), external beam radiotherapy (RT), or radical prostatectomy (RP) were evaluated. Methods: From 1996 to 2003, 2285 patients with low or intermediate-risk CaP were treated at the Cleveland Clinic with either PI (n=662), RT (n=570), or RP (n=1053). Factors thought to influence OS and CSS were recorded. These factors included: Charlson score, age, socioeconomic status, race, body mass index (BMI), presence of coronary artery disease (CAD), presence of hypertension (HTN), presence of dyslipidemia (DL), initial prostate-specific antigen (iPSA), biopsy Gleason score (bGS), clinical stage, use of androgen deprivation (AD), AD duration, smoking history including pack-years, alcohol use, and cancer treatment modality (TX). Univariate and multivariate analyses were done using Cox proportional hazards regression. Results: The median follow-up is 59 months (range: 24–119 months). The 5- year OS rate is 96.0%, and the 8-year rate is 89.9%. Multivariate analysis revealed that Charlson score, age, smoking history, and TX were significantly associated with OS. Treatment with RT was independently associated with worse OS relative to PI and RP. CSS was grouped into 4 major categories: CAD, CaP, other cancer, and other. The only significant difference between these CSS categories and the treatment modalities was CaP. The percent of deaths due to CaP in the TX groups were: PI - 3.2%, RP - 9.7%, and RT - 24.5%. Conclusions: Charlson score, age, smoking history, and TX independently affect OS in patients treated for low and intermediate-risk CaP. The cause of the lower OS rate with RT may be related to an increased risk of death due to CaP. [Table: see text] No significant financial relationships to disclose.
Phase II trial of oxaliplatin, pemetrexed, and bevacizumab in previously-treated advanced non-small cell lung cancer (NSCLC)
Authors: R. S. Heist, P. Fidias, M. Huberman, J. Temel, L. Sequist, T. J. Lynch
Journal: Journal of Clinical Oncology (2007)

7700 Background: Single agent chemotherapy is standard for second and third line therapy of NSCLC. Combination therapy has to date not proven to be superior to single agents –often adding additional toxicity without any additional efficacy. We investigated whether the combination of oxaliplatin, pemetrexed, and bevacizumab was an active and tolerable regimen in the pre-treated advanced NSCLC setting. Methods: In this two-stage phase II trial, patients received pemetrexed (500 mg/m2), oxaliplatin (120 mg/m2), and bevacizumab (15 mg/kg) on day 1 of every 21 day cycle, for a total of 6 cycles or until disease progression. Eligibility criteria included PS 0–1, non-squamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed on this trial. The primary endpoint was response rate, with secondary endpoints of TTP, PFS, and OS. Results: 36 patients were enrolled on this study. Patient characteristics for 32 for which data is available were: 16 (50%) women, 16 (50%) men, 26 (81%) adenocarcinoma, 6 (19%) large cell or NSCLC, 6 (19%) treated brain metastases. Of the 31 patients evaluable for tumor response, 0 had CR, 8 (25%) had PR, 14 (44%) had SD, and 9 (28%) had PD. One patient experienced Grade V hemoptysis after cycle 2 before restaging. Nine patients experienced a Grade III/IV serious adverse event. These Grade III/IV toxicities included: cardiac ischemia (1), sensory neuropathy (1), dyspnea (1), anemia (1), constipation (1), fatigue (1), colitis (1), face pain (1), hyperglycemia (1), elevated ALT (1). Among the 6 patients with treated brain metastases, there was 1 PR, 2 SD, 2 PD, and one patient with Grade V hemoptysis whose response could not be assessed; there were no brain hemorrhage events. Data for PFS and OS are preliminary; estimated median PFS is 5.8 months (95% CI 3.8 - 8.9 mo), and estimated OS is 10.9 mo (95% CI 6.4 - 20 mo). Updated data will be presented at the time of the meeting. Conclusions: This data suggests that the combination of pemetrexed, oxaliplatin, and bevacizumab is tolerable and has a promising response rate. Updated data will be presented at the meeting. No significant financial relationships to disclose.
Significance of cytogenetic clonal evolution in chronic myelogenous leukemia.
Authors: A Majlis, T L Smith, M Talpaz, S O'Brien, M B Rios, H M Kantarjian
Journal: Journal of Clinical Oncology (1996)

PURPOSE To describe the incidence and significance of clonal evolution patterns. PATIENTS AND METHODS We analyzed 264 patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed clonal evolution between 1967 and 1993. RESULTS The median survival time following clonal evolution was 19 months. Factors associated with worse survival (P &lt; .01) were as follows: chromosome 17 abnormality or chromosomal translocations other than Ph, high percentage of abnormal metaphases, longer time to clonal evolution, and presence of other accelerated-phase features. A recursive partitioning technique (CART) identified different risk groups. The best group (37 patients; no chromosome 17 abnormality, abnormal metaphases &lt; 16%, and interval to clonal evolution &lt; or = 24 months) had an estimated median survival time of 54 months. The worst two groups included 27 patients with chromosome 17 abnormalities and &gt; or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22 patients with other accelerated features and &gt; or = 16% abnormal metaphases (estimated median survival time, 7 months). The intermediate group had an estimated median survival time that ranged from 13 to 24 months. Prior interferon therapy evaluated within risk groups showed a significant survival advantage only in the intermediate-risk group. A multivariate analysis showed similar results, and identified the following independent poor prognostic variables: chromosome 17 abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to clonal evolution (cutoff, 24 months), other accelerated-phase features, and no prior interferon therapy. Patients with none, one, two, three, or more of the first four features had median survivals times of 51, 24, 14, and 7 months, respectively. CONCLUSION The prognostic significance of clonal evolution in CML is not uniform and is related to the specific abnormality, time to its development, its predominance in metaphases, and the presence of other accelerated features, and it may be modified by specific therapies.
William Paul Butt
Authors: P. J. A. Robinson
Journal: BMJ (2015)

William Paul Butt, who died in September, was pre-eminent in musculoskeletal radiology, initially in his native Canada, then later in the UK and Europe after his move to Leeds in 1979.

He described his childhood background as one of poverty; this became the uncompromising driving force behind his striving for education and his thirst for knowledge. He worked in a supermarket to finance his medical training, qualifying in Toronto in 1959. His radiology training in the mid 1960s included fellowships in London, Oxford, Edinburgh, and Gothenburg; during this period he was admitted as a fellow of the Faculty of Radiologists, as the royal college was then styled. Appointed to the staff of Montreal General Hospital, he developed particular expertise in skeletal radiology, publishing on discography and other spine related topics.

Paul had a direct and robust approach that led him to become dissatisfied with the niceties of medical politics, and he left …
Nolatrexed dihydrochloride vs. doxorubicin, a clinical update of a multi-center randomized phase II study (014) in ethnic Chinese subjects with unresectable or metastatic HCC
Authors: J. Gallo
Journal: Journal of Clinical Oncology (2004)

4262 Background: Initial results of the original multi-center randomized Phase II study reported by Mok et al suggested that there was a 41% difference in the median survival of THYMITAQ (T) over doxorubicin (dox). We hereby present updated median survivals for the intent-to-treat (ITT) and evaluable populations within the same trial and a review of the patients' clinical characteristics in this particular trial. Methods: 54 patients were randomized in a 2:1 fashion to receive either T (37) or dox (17), respectively. 44 subjects who completed 2 or more cycles of either drug were considered for the evaluable population. The clinical presentation of these patients is reviewed. Results: For the ITT population, the median survival for the T arm was 19.8 wks and the dox arm was 14.8 wks, which represents a 34% increase in median survival in favor of T. The evaluable population for T produced a median survival of 23.4 wks compared to a median survival of 15.4 wks for dox, which represents a 52% increase in survival in favor of T. Of the 54 patients in the trial, 32 (59%) had cirrhosis, 22 of these in the T arm and 10 in the dox arm. In addition, 26 (48%) had portal invasion; 42 (78%) were hepatitis carriers. Conclusions: As noted in the previous communication of study 014 there is a difference in median survival in favor of T vs. dox. Although the p value (0.8519) on median survival was not significant; there was clinical benefit in terms of survival, particularly evident when the patient characteristics of each treatment arm are reviewed. Cirrhosis, portal invasion and hepatitis carriers have the worst outcomes in terms of survival in HCC. Regardless of these bad prognosis factors patients treated with T did better in terms of survival than those treated with dox (by 34% in ITT population and by 52% in evaluable population). The randomization in the current ETHECC (Evaluation of T in HCC) Phase III study is based on CLIP scores and Karnofsky PS which allows for an equal distribution of patients characteristics at randomization. The primary endpoint of ETHECC is overall survival in the treatment of unresectable HCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration EXIMIAS Pharmaceutical Corp.
The role of health literacy in patient navigation intensity prior to and post-prostate cancer diagnosis
Authors: M. A. Simon, N. J. Nonzee, J. M. McKoy, A. Rademaker, P. J. Byer, J. Feinglass, E. A. Calhoun, J. Darnell, R. Massenburg, C. L. Bennett
Journal: Journal of Clinical Oncology (2008)

17534 Background: Patient navigator research programs (PNRP) are evaluating barriers to care among low-income patients with a positive cancer screening test. Health literacy may be one domain that impacts navigation provision. We reviewed pilot data on health literacy and intensity of care coordination required among Veterans with an abnormal prostate cancer screen. Methods: Social worker and lay health navigators recorded patient and system barriers to follow-up care, length of patient encounters, and case management actions. Navigation began after notification of an abnormal prostate cancer screen and carried through diagnostic resolution or through the first course of treatment. Literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM-7). Results: Of the navigated 27 patients, 5 had cancer; 33% had a low health literacy level of ≤8th grade; all successfully completed a biopsy. Among patients with cancer, navigation effectively resulted in a 100% treatment completion rate (3 RP, 1 WW, 1 undecided) and a median of 76 days between diagnosis and start of treatment. Navigators spent over twice as much time interfacing with patients with cancer including greater median in-person encounters and twice as many phone encounters as patients without cancer (p=0.002, 0.008, and 0.001, respectively). The difference in navigation provision time between those patients with high versus low literacy was insignificant. Patient navigators’ most common case management actions included providing emotional support and appointment reminders. Conclusion: Health literacy was not an indicator of navigation intensity for this pilot cohort. Future studies should focus on customization of delivery of cancer care services with respect to patients with low literacy and follow-up compliance. Navigation intensity for patients undergoing prostate cancer screening and treatment N (%) Median navigation time per patient in minutes (SIQR) Median encounters per patient (SIQR) Median in-person encounters per patient (SIQR) Median phone encounters per patient (SIQR) All patients 27 (100) 95 (27.5) 8 (2.5) 3 (0.5) 6 (3) Cancer patients 5 (19) 200 (37.5)* 14 (4.5)* 4 (1)* 9 (4)* pre-diagnosis 5 (19) 65 (10) 5 (0.5) 1 (0.5) 2 (1) post-diagnosis 5 (19) 135 (35) 10 (1) 2 (1) 8 (1) Non-cancer patients 22 (81) 88 (20) 7 (1) 3 (0.5) 5 (1.5) * p < 0.05 No significant financial relationships to disclose.
Dscam Proteins Direct Dendritic Targeting through Adhesion
Authors: Wael Tadros, Shuwa Xu, Orkun Akin, Caroline H. Yi, Grace Ji-eun Shin, S. Sean Millard, S. Lawrence Zipursky
Journal: Neuron (2016)

Cell recognition molecules are key regulators of neural circuit assembly. The Dscam family of recognition molecules in Drosophila has been shown to regulate interactions between neurons through homophilic repulsion. This is exemplified by Dscam1 and Dscam2, which together repel dendrites of lamina neurons, L1 and L2, in the visual system. By contrast, here we show that Dscam2 directs dendritic targeting of another lamina neuron, L4, through homophilic adhesion. Through live imaging and genetic mosaics to dissect interactions between specific cells, we show that Dscam2 is required in L4 and its target cells for correct dendritic targeting. In a genetic screen, we identified Dscam4 as another regulator of L4 targeting which acts with Dscam2 in the same pathway to regulate this process. This ensures tiling of the lamina neuropil through heterotypic interactions. Thus, different combinations of Dscam proteins act through distinct mechanisms in closely related neurons to pattern neural circuits.
Virus-Like Particles in Human Plasma and Serum: Role of Platelet Lysosomes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Alfred M. Prince, W. Robert Adams
Journal: JNCI Journal of the National Cancer Institute (1966)

Virus-like particles, similar to those described in human leukemic sera by many investigators, were found and quantitated in plasmas and sera from patients with leukemia and hepatitis and from controls. The association of at least the major fraction of these particles with pathologic sera was found to be artifactual, reflecting delay in separation from cellular elements in blood. These particles were identified as a specific lysosomal granule of the platelet. The ultrastructure of phosphotungstic acid- and uranyl acetate-stained preparations is illustrated. Although these studies emphasize the necessity for extreme caution in ascribing a viral nature to the virus-like particles described in human leukemic sera and plasma, the possibility should not be ruled out that some true virus particles have been identified and that their structure may closely resemble that described here. Immunologic or biologic techniques are, however, required before such a conclusion can be established.
Abediterol has higher β2-receptor affinity and in vitro bronchodilatory potency than other long-acting β2-agonists, with good selectivity
Authors: Montserrat Miralpeix, Mònica Aparici, Carla Carcasona, Israel Ramos, Carlos Puig, Dolors Vilella, Amadeu Gavaldà
Journal: European Respiratory Journal (2014)

Introduction 

Abediterol (LAS100977) is a novel, long-acting, inhaled s2-receptor agonist in Phase II development for asthma and COPD. We report the in vitro potency, selectivity and duration of action (DoA) of abediterol vs indacaterol, olodaterol and vilanterol.

Methods 

Affinity studies used chinese hamster ovary cells expressing human, guinea pig (GP) or dog β1 or β2 receptors. Potency, onset and DoA were assessed in vitro in GP trachea. Onset (time to 50% maximal relaxation) and DoA (time to 50% recovery of maximal contraction) were assessed at IC80 concentration. β1-receptor activity was assessed in GP left heart atria at cumulative concentrations (1 nM–10 μM).

Results 

Abediterol had the highest s2-receptor affinity vs comparators; all compounds had substantially lower s1-receptor affinity (Table). The potency of abediterol (0.1 nM) was 5-, 77- and 80-fold greater than olodaterol, indacaterol and vilanterol, respectively. Abediterol had slightly slower onset vs comparators. DoA of abediterol was similar to vilanterol (both >480 min) and longer than indacaterol (218 min) and olodaterol (325 min). Abediterol, olodaterol and vilanterol all had very low potency in atrial tissue (EC50 >10 μM), vs 6.3 μM for indacaterol.

Conclusion 

Abediterol is a potent s2-receptor agonist with a long DoA in tracheal tissue and low activity in atrial tissue, suggesting that abediterol may offer reduced potential for cardiac effects in humans.

View this table:

Receptor affinity IC50 (nM)
Prone accelerated partial breast irradiation (five fractions) after breast conservation therapy with heart and lung sparing
Authors: S. C. Formenti, J. Goldberg, B. Rosenstein, K. Dewyngaert
Journal: Journal of Clinical Oncology (2004)

870 Background: The convenience of a shorter course of adjuvant radiation after breast conservation therapy (BCT) has encouraged the exploration of partial breast radiation techniques. We are reporting the clinical and physical results of the first 47 patients accrued to an ongoing accelerated partial breast irradiation (APBI) protocol utilizing three dimensional conformal radiation therapy (3D-CRT) in prone position after BCT ( supported by DOD DAMD 17–01-1–0345). Methods: A regimen of external beam conformal hypo-fractionated radiotherapy directed to the original tumor bed with margins was prospectively tested in a phase I/II study. Post-menopausal women with non-palpable T1N0 breast cancer, excised with at least 5 mm margins, lack of EIC, and receptor positive tumors were offered eligibility to the study only if they had first refused six weeks of standard radiation. Planning CT and treatment were performed in the prone position, on a dedicated table to best spare heart and lung tissues. The planning target volume (PTV) was defined at CT as the post-excisoinal surgical cavity plus a 2 cm margin(Varian Somavision/CadPlan/Eclipse). Based on radiobiological modeling, the prescribed dose (PD) was 6 Gy per fraction delivered to the 95% isodose surface in 5 fractions over ten days to a total dose of 30 Gy. A 2-stage Simon design with projected enrollment of at most 99 patients was used (significance level of 0.05 and power of 0.80). Results: 47 patients have completed treatment. Median age is 67.5 years (51 –85) and median tumor diameter is 1 cm (0.2–1.9). Acute effects were limited to Grade 1–2 erythema in 22/47 patients (47%). The mean volume of the ipsilateral breast (IBV) receiving 100% of the PD was 26% (range 10–45%). The mean volume receiving 50% of the PD was 47% (range 23–75%). In all patients no significant heart or lung volume was treated by the prone technique. At a median follow-up of 2 years, no patient has recurred. Conclusions: These preliminary data support the feasibility of prone APBI, which is well tolerated and enables heart and lung sparing. Longer follow-up is required to assess efficacy and long term cosmetic results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Department of Defense DAMD17–01-1–0345; 2001–2004 P.I.Formenti, S.C.
Microarray screening and microsatellite analysis suggest the significance of allelic imbalance of 19p-region in asbestos-associated lung cancer
Authors: Salla Ruosaari, Harriet Wikman, Penny Nymark, Esa Vanhala, Antti Karjalainen, Jaakko Hollmen, Sakari Knuutila, Sisko Anttila
Journal: Cancer Research (2007)

4993   Occupational exposure to asbestos is associated with the development of asbestosis, malignant mesothelioma, and lung cancer. Asbestos fibers have been shown to act as genotoxic and cytotoxic agents that can produce both DNA and chromosomal damage. Both direct and indirect interaction of asbestos fibers and target cells are assumed to lead to DNA damage despite the exact mechanisms are yet to be discovered.  We performed DNA copy number and gene expression microarrays on lung tumor samples from 14 highly asbestos-exposed and from 14 non-exposed patients with the aim to identify potential asbestos-associated aberrations. To identify chromosomal regions with DNA copy number and expressional differences between the tumors of exposed and non-exposed patients, the gene expression data was combined with CGH microarray data and analyzed at group level. The identification of exposure-related areas was performed by using overlapping 0.5-1 Mbp segments, and each segment was tested for differences in copy numbers and gene expression between the exposed and non-exposed groups. The exposure-associated regions were identified by means of hypothesis testing.  By combining the gene expression data with the DNA copy number data, we identified six chromosomal regions showing association to asbestos-exposure on both DNA and mRNA level. One of these regions, namely 19p13.3.-13.1, was further characterized by microsatellite analysis in 62 patients for allelic imbalance differences between tumors of non-exposed and exposed patients. Our results suggest that the loss of the 19p-region is significantly associated with asbestos-exposure. Furthermore, in tumors of asbestos-exposed patients, AI in 19p seems to appear regardless of the histological tumor type whereas in tumors of non-exposed patients AI is more restricted to certain tumor types.
Abstract 18319: The Impact of Low Grade Urinary Albumin on the Risk of Cardiovascular Disease in the Nonhypertensive and Nondiabetic Population
Authors: Fumitaka Tanaka, Shinji Makita, Toshiyuki Onoda, Kozo Tanno, Masaki Ohsawa, Kazuyoshi Itai, Kiyomi Sakata, Shin-ichi Omama, Kuniaki Ogasawara, Yasuhiro Ishibashi, Akira Okayama, Motoyuki Nakamura
Journal: Circulation (2014)

Background: The guidelines recommend screening for microalbuminuria in patients with hypertension and diabetes. Recent cohort studies document a continuous association between low grade urinary albumin (UA) and increased risk of cardiovascular disease (CVD) in these patient groups. However, it is unclear whether this association is present in individuals without hypertension and diabetes. Hypothesis: Even in the nonhypertensive and nondiabetic population, UA from low levels may be related to future CVD risk. Methods: A population-based prospective cohort study was performed in 13,451 nonhypertensive, nondiabetic individuals aged 40 to 89 years (mean age = 60.4±10.2 years) with no cardiovascular history. A multivariate Cox regression analysis was performed to examine the relationship between quartile of urinary albumin/creatinine ratios (UACRs) and the incidence of CVD which was defined as stroke or acute myocardial infarction/sudden cardiac death. Results: During a mean follow-up period of 5.6 years, 213 ...