tbuckley/cabot-search huggingface dataset:
Scoring systems predictive of survival and local control of patients irradiated for brain metastases
Authors: L. Dziggel, T. Veninga, T. Haatanen, R. Lohynska, S. E. Schild, S. E. Schild, D. Rades
Journal: Journal of Clinical Oncology (2009)

2075 Background: This study was performed to create and validate scoring systems to estimate survival and intracerebral local control at 6 months of patients irradiated for brain metastases. Methods: Data of 1,797 patients irradiated for brain metastases (1,346 whole-brain radiotherapy [WBRT], 131 radiosurgery [RS], 61 WBRT + RS, 259 resection + WBRT) were retrospectively analyzed. Patients were randomly assigned to the test group (N = 1,198) or the validation group (N = 599). In the test group, multivariate analyses (MVA, Cox proportional hazards model) were performed for survival (OS) and local control (LC). Based on the MVA results, two scoring systems were developed, one for OS and another for LC. The scores included the prognostic factors found significant on MVA. Age, performance status, extracranial metastases, interval from tumor diagnosis to RT, and number of brain metastases were significant for OS. Tumor type, performance status, interval from tumor diagnosis to RT, and number of brain metastases were significant for LC. The score for each factor was determined by dividing the 6-month OS or LC rate (%) by 10. The total score represented the sum of the scores for each factor. For OS, total scores ranged from 15–30 points, and patients were divided into three groups (15–19, 20–25, and 26–30 points). For LC, total scores ranged from 14–27 points, and patients were divided into three groups (14–18, 19–23, and 24–27 points). Results: In the test group, the 6-month OS rates were 9 ± 1% for patients with scores of 15–19 points, 41 ± 2% for those with 20–25 points, and 78 ± 2% for those with 26–30 points (p &lt; 0.0001). The corresponding OS rates in the validation group were 7 ± 2%, 39 ± 3%, and 79 ± 3%, respectively (p &lt; 0.0001).In the test group, the 6-month LC rates were 17 ± 3% for patients with 14–18 points, 49 ± 3% for those with 19–23 points, and 77 ± 2% for those with 24–27 points (p &lt; 0.0001). The corresponding LC rates in the validation group were 19 ± 4%, 52 ± 4%, and 77 ± 3%, respectively (p &lt; 0.0001). Conclusions: Patients irradiated for brain metastases can be grouped with these scores to estimate OS and LC. The OS and LC rates of the validation group were almost identical to the test group, which demonstrates the high validity and reproducibility of both scores. No significant financial relationships to disclose.
Top2A FISH with cytokeratin discriminators in breast cancer using automated high throughput analysis.
Authors: D. T. Weaver, W. Pierceall, K. M. Sprott, T. Heikkinen, P. Heikkila, J. Bartek, C. Blomqvist, H. Nevanlinna
Journal: Journal of Clinical Oncology (2010)

e11061 Background: Biomarker profiling increasingly provides key information for discriminating good versus poor outcome in chemotherapy treatment decisions (personalized medicine). For breast cancer patients treated with anthracycline-based regimens, tumor TOP2A expression levels examined by IHC are not as predictive of overall survival as TOP2A gene copy alterations. The SWOG S9313/Int0137 study report suggests that TOP2A status is not predictive of recurrence with anthracycline-based regimens. We examined TOP2A by a FISH-based approach in a large breast cancer study and stratified patients for analysis by therapy (anthracycline-based with radiation therapy (RT), nonanthracycline -based with RT or RT alone). Methods: FFPE specimens were configured on Tissue Microarrays (TMAs) for efficient analysis. 1,491 breast cancer patient tumors (4 cores/patient; 0.6 mm diameter, 5 um thickness) were evaluated for TOP2A status by FISH coupled with cytokeratin (CK, clone AE1/AE3) immunofluorescence (IF). All slides were subjected to FISH with Dako TOP2A (Texas Red) and centromeric CEN17 (FITC) probes. Following probe hybridization, IF was performed to identify positive staining cells for scoring. Stained tissue was imaged and analyzed on a Metafer/Metacyte (Metasystems) automated platform with a customized image classifier for high throughput analysis. 20-60 cells were scored for each sample. Approximately 60% of the samples were of sufficient quality to be considered informative. Results: We have developed a novel FISH/IF approach for increased scoring throughput, whereby tumor zones are identified by IF staining. TOP2A:CEN17 ratios ranged from 0.4 to 3.9, indicative of genetic instability (evidenced by amplifications/deletions) of the TOP2A locus. A TOP2A:CEN17 ratio of > 2.0 (amplified) and < 0.8 (deleted) were observed for approximately 6% and 12% of the patients respectively. Conclusions: We have established an improvement to the TOP2A measurement where the combination of cytokeratin discrimination of tumor zones leads to more effective TOP2A:CEN17 determinations. No significant financial relationships to disclose.
Low oxygen tension enhances the generation of lung progenitor cells from mouse embryonic and induced pluripotent stem cells
Authors: Elena Garreta, Esther Melo, Daniel Navajas, Ramon Farre
Journal: European Respiratory Journal (2014)

Whole-organ decellularization technology has emerged as a new alternative for the fabrication of bioartificial lungs. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) are potentially useful for recellularization since they can be directed to express phenotypic marker genes of lung epithelial cells. Normal pulmonary development takes place in a low oxygen environment ranging from 1 to 5%. By contrast, in vitro ESC and iPSC differentiation protocols are usually carried out at room-air oxygen tension. Here, we sought to determine the role played by oxygen tension on the derivation of Nkx2.1+ lung/thyroid progenitor cells from mouse ESC and iPSC. A step-wise differentiation protocol was used to generate Nkx2.1+ lung/thyroid progenitors under 20% and 5% oxygen tension. On day 12, gene expression analysis revealed that Nkx2.1 and Foxa2 (endodermal and early lung epithelial cell marker) were significantly upregulated at 5% oxygen tension in ESC and iPSC differentiated cultures compared to 20% oxygen conditions. In addition, quantification of Foxa2+Nkx2.1+Pax8- cells corresponding to the lung field, with exclusion of the potential thyroid fate identified by Pax8 expression, confirmed that the low physiologic oxygen tension exerted a significant positive effect on early pulmonary differentiation of ESC and iPSC. In conclusion, we found that 5% oxygen tension enhanced the derivation of lung progenitors from mouse ESC and iPSC compared to 20% room-air oxygen tension.
肥胖的预后——我们都需要多动些、少吃些
Authors: 李玉秀（译）
Journal: BMJ (2005)

肥胖已对世界很多地区人们的躯体、精神以及社交产生了巨大的影响。如果不采取有效的措施，老年人群的腰围不断增加，其相关健康问题将会给未来几代人带来巨大的经济负担。肥胖的患病率已经突破15％——世界卫生组织（WHO）设定的需要干预的流行性疾病阈值。。我们不能减少对肥胖个体的医疗支持，但是我们更急需政策措施来改善公共健康，阻止其流行趋势。
Changes to the hormone receptor expression in patients treated with either tamoxifen or aromatase inhibitors as endocrine therapy for breast cancer
Authors: S. Djahansouzi, V. Rostock, D. Niederacher, W. Rath, H. Bender, B. Hanstein
Journal: Journal of Clinical Oncology (2006)

10543 Background: Endocrine therapy (ET) of patients with hormone receptor (HR)-positive breast cancer (BC) is thought to adversely affect the HR expression of the tumor with time. In order to evaluate this, a study was undertaken comparing the HR status prior to adjuvant Tamoxifen (Tam) therapy and after progression in estrogen receptor (ER)-positive BC patients. Similarly, ET with aromatase inhibitors (AI) was investigated by comparing the HR status prior to AI therapy and after progression in ER-positive metastatic BC patients. Methods: A retrospective analysis of all stage I-III ER-positive BC patients who presented to the department between 1999 to 2004 and received adjuvant Tam for ≥ 6 month and had the tumor relapse (local recurrence or distant metastasis) confirmed by tumor biopsy. All patients were evaluated for ER and progesterone receptor (PR) status prior to ET as well as after relapse using immunohistochemistry. Similarly, stage IV ER-positive metastatic BC patients who received AI for ≥ 3 month with tumor biopsy prior and after AI therapy, were also analyzed in regards to their HR expression. Results: 44 eligible ER-positive BC patients constituted the Tam group. After relapse, 55% of the patients remained ER-positive, while 45% lost their positive ER status. For PR, 34 out of 44 patients were initially receptor positive (77%). Similarly, 15 out of 34 patients retained a positive PR expression (44%) and the 10 PR-negative patients showed no change in receptor expression following Tam. 5 eligible patients with ER-positive metastatic BC constituted the AI group. After progression, 4 out of 5 patients remained receptor positive, while 1 patient lost ER expression. For PR, 3 out of 5 patients were initially PR positive. After AI, only 2 patients showed a positive PR status. 2 patients were PR negative before and after AI therapy. Conclusions: Contrary to the belief that clinical progression under ET is probably as a result of the loss of HR expression, our data suggests that progression under ET does not necessarily result in the loss of HR expression. In fact, 55% of relapses under Tam and 80% of the progressions under AI remain ER positive, indicating potential susceptibility to other endocrine therapeutic agents. No significant financial relationships to disclose.
Do women with primary breast cancer who experience chemotherapy-induced menopause have worse symptoms than those due to natural menopause?
Authors: N. Tchen, H. Mar Fan, Q.-L. Yi, I. Chemerynsky, J. Galica, K. Sabate, I. F. Tannock
Journal: Journal of Clinical Oncology (2005)

8016 Background: Women receiving chemotherapy may have accelerated menopause. It is not known whether their menopausal symptoms are more severe than in (older) women undergoing a natural menopause. Methods: In this comparative study women with chemotherapy-induced menopause were compared with healthy women having recent menopause. Recent menopause was defined by last period >6 and <24 months prior to recruitment. Patients were a subset of those receiving adjuvant chemotherapy for breast cancer recruited to a prior study (Tchen et al: J Clin Oncol 2003;21:4175–83). Controls were either healthy participants in the prior study, or were recruited from a breast cancer screening program. Subjects were evaluated on 3 occasions 1 year (+/−2 months) apart and the primary evaluation for patients was at ∼1 year after end of chemotherapy. Subjects completed the FACT-G Quality of Life questionnaire with its subscales for endocrine (menopausal) symptoms (FACT-ES) and fatigue (FACT-F). Cognitive function was evaluated by the High Sensitivity Cognitive Screen (HSCS). Subjects were asked to donate blood for determination of estradiol, LH and FSH. The primary endpoint was the FACT-ES score. Results: For the primary comparison, median time since last period was 16 months for patients (N=41) and 17 months for controls (N=46, p=0.6). Median values for outcome measures are summarized in the table (higher values indicate better function). Follow-up data will be presented at the meeting.Conclusions: Patients with chemotherapy-induced menopause have worse symptoms than women experiencing a normal menopause. No significant financial relationships to disclose.
Should Patients Have Periodic Health Examinations?
Authors: Eileen E. Reynolds, James Heffernan, Ateev Mehrotra, Howard Libman
Journal: Annals of Internal Medicine (2016)

Physicians and patients have come to expect that periodic health examinations (PHEs) are a standard part of comprehensive ongoing medical care. However, considerable research has not demonstrated a substantial benefit of the PHE. Given this lack of benefit and the high total cost of PHE to the health care system, the American Board of Internal Medicine (ABIM) Foundation and the Society of General Internal Medicine (SGIM) have identified “routine health checks in asymptomatic patients” as something of low value that physicians and patients should question, as a part of the Choosing Wisely campaign. Two discussants review the debate about PHE and consider the value of PHE for a healthy 70-year-old woman who appreciates seeing her physician annually.
Clinical and cytogenetic responses to amonafide in secondary acute myeloid leukemia (AML)
Authors: S. L. Allen, J. E. Kolitz, A. S. Lundberg, R. L. Capizzi, D. R. Budman
Journal: Journal of Clinical Oncology (2006)

6584 Background: Patients (pts) with secondary AML (AML following an antecedent hematologic disorder or following known exposure to leukemogenic agents) are often elderly, with comorbid illness, and have a dismal prognosis. Secondary AML responds poorly to standard chemotherapy, with low response rates and short durations of remission. Amonafide (Am) is an ATP independent topoisomerase 2 inhibitor that in prior clinical studies had myelosuppression as the dose-limiting toxicity. Two phase 1 trials evaluated Am as either a single agent or in combination with ara-C in pts with relapsed/refractory or secondary AML. This retrospective review was performed to assess the activity of Am specifically in pts with secondary AML. Methods: In study AM-03, 5 pts with secondary AML were treated with a fixed dose (1000, 1100, or 1400 mg/m 2 /day) of Am IV over 2 hrs daily × 5. In study AM-04, 15 pts with secondary AML were treated with ara-C 200 mg/m 2 /day CIV days 1–7 and a fixed dose (600, 700 or 800 mg/m 2 /d) of Am IV over 2 hrs daily on days 1–5. All clinical trial data were reviewed for assessment of hematological and cytogenetic response. Results: Across the two studies, 10 of 20 (50%) pts responded to Am (9 CR, 1 CRi). In study AM-03 (Am monotherapy), 3 of 5 (60%) pts responded, with median duration of response 7.5 months (range 2.5 - 8). None of these 3 pts received additional post-remission therapy. In study AM-04 (Am + ara-C), 7 of 15 pts (47%) responded, with median duration of response 8 months (range 1 ¾ to &gt;60 months). 4 of these 7 pts received additional post-remission therapy. Cytogenetic analysis prior to and following Am therapy was available for 9 of the 10 pts with secondary AML who responded to Am in the 2 studies. Cytogenetics were abnormal prior to Am therapy in 5 of these 9 pts, 3 (60%) of whom achieved cytogenetic CR. Conclusions: Am shows significant activity in secondary AML, both as monotherapy and in combination with ara-C. A phase 2 trial of Am + ara-C in pts with secondary AML is currently enrolling patients. [Table: see text]
Abstract 19384: Favorable Association Between a Mediterranean Dietary Pattern and Cardiovascular Risk Factors in Patients with Stable Coronary Heart Disease in the STABILITY Study
Authors: Ralph A Stewart, Lars Wallentin, Jocelyne Benatar, Nicolas Danchin, Emil Hagström, Robert A Harrington, Claes Held, Steen Husted, Eva Lonn, Amanda Stebbins, Ola Vedin, David Watson, Havey D White
Journal: Circulation (2014)

Introduction: A ‘Mediterranean’ dietary (MD) pattern has been associated with lower cardiovascular mortality, but the reasons for benefit are uncertain. Hypothesis: Greater adherence to a MD pattern is associated with more favorable cardiovascular risk factors. Methods: Associations between a MD pattern and cardiovascular risk factors were evaluated at the baseline assessment in 15,482 (97.8%) patients with chronic coronary heart disease from 39 countries who participated in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial. From a food frequency questionnaire a Mediterranean Diet Score (MDS) was calculated by assigning points for more consumption of whole grains, fruits and vegetables, legumes, fish and alcohol, and for less consumption of meat (0 to 4 points in each food category). Cardiovascular risk factors at baseline are reported by approximate quartiles of MDS. Results: See table. For all risk factors p was &lt;0.0001 for differences by MDS group. Conclusions: In a global population of patients with stable CHD greater adherence to a MD pattern was associated with less obesity, less hypertension, improved glucose tolerance and less inflammation.
Variations in mitochondrial tRNA gene organization of reptiles as phylogenetic markers.
Authors: Y Kumazawa, M Nishida
Journal: Molecular Biology and Evolution (1995)

Amplification and sequencing of mitochondrial DNA regions corresponding to three major clusters of transfer RNA genes from a variety of species representing major groups of birds and reptiles revealed some new variations in tRNA gene organization. First, a gene rearrangement from tRNA(His)-tRNA(Ser)(AGY)-tRNA(Leu)(CUN) to tRNA(Ser)(AGY)-tRNA(His)tRNA(Leu)(CUN) occurs in all three crocodilians examined (alligator, caiman, and crocodile). In addition an exceptionally long spacer region between the genes for NADH dehydrogenase subunit 4 and tRNA(Ser)(AGY) is found in caiman. Second, in congruence with a recent finding by Seutin et al., a characteristic stem-and-loop structure for the putative light-strand replication origin located between tRNA(Asn) and tRNA(Cys) genes is absent for all the birds and crocodilians. This stem-and-loop structure is absent in an additional species, the Texas blind snake, whereas the stem-and-loop structure is present in other snakes, lizards, turtles, mammals, and a frog. The disappearance of the stem-and-loop structure in the blind snake most likely occurred independently of that on the lineage leading to birds and crocodilians. Finally, the blind snake has a novel type of tRNA gene arrangement in which the tRNA(Gln) gene moved from one tRNA cluster to another. Sequence substitution rates for the tRNA genes appeared to be somewhat higher in crocodialians than in birds and mammals. As regards the controversial phylogenetic relationship among the Aves, Crocodilia, and Mammalia, a sister group relationship of birds and crocodilians relative to mammals, as suggested from the common loss of the stem-and-loop structure, was supported with statistical significance by molecular phylogenetic analyses using the tRNA gene sequence data.
Plasma and tumor tissue pharmacology of high-dose intravenous leucovorin calcium in combination with fluorouracil in patients with advanced colorectal carcinoma.
Authors: F Trave, Y M Rustum, N J Petrelli, L Herrera, A Mittelman, C Frank, P J Creaven
Journal: Journal of Clinical Oncology (1988)

Plasma pharmacokinetics of high-dose (500 mg/m2) leucovorin calcium (dl-5-formyltetrahydrofolic acid [dl-CF]) and fluorouracil (FUra) have been evaluated in patients with advanced colorectal cancer treated with the combination of FUra and dl-CF by two different intravenous (IV) schedules: (A) In patients with no prior chemotherapy, dl-CF was administered by a two-hour IV infusion and FUra by rapid IV injection one hour after the start of the dl-CF infusion and (B) in previously treated patients, dl-CF and FUra were administered by five-day continuous IV infusion (CI). Following the two-hour infusion of dl-CF, mean peak plasma concentration and elimination half-life of I-5-formyltetrahydrofolic acid (I-CF) were 24 +/- 6 mumol/L and 0.8 +/- 0.1 hour, respectively. CI of dl-CF over five days yielded a mean steady-state plasma level of I-CF of only 1.2 +/- 0.5 mumol/L. Peak and steady-state plasma concentrations of the metabolite 5-methyl tetrahydrofolic acid were comparable in the two schedules (17 +/- 8 mumol/L for the two-hour infusion and 12 +/- 5 mumol/L for the CI). Areas under the concentration v time curve (AUC) of total reduced folates were significantly greater under conditions of CI: 89.0 v 16.7 mmol/L/min for the two-hour infusion. In tumor tissue, 5,10-methylenetetrahydrofolate increased eight-fold two to four hours following the two-hour infusion and two-fold during the CI of dl-CF and FUra. Inhibition of thymidylate synthase (dTMP-S) by the two-hour and CI infusion schedules were 66% v 39%, respectively. The observed differences in the intracellular dTMP-S folate cofactor pools and the degree of inhibition of dTMP-S achieved in patients treated by two different schedules may be due to differences in the biochemical properties and/or to differences in the modulation of FUra metabolism by folate of tumor tissues obtained from newly diagnosed and previously treated patients.
UK is safe from Zika virus and is helping towards a vaccine, MPs hear
Authors: Adrian O’Dowd
Journal: BMJ (2016)

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Rituximab plus gemcitabine and oxaliplatine (R-GemOx) in refractory/relapsed patients with diffuse large B-cell lymphoma (DLBCL) who are not candidates for high-dose therapy (HDT): A GELA study.
Authors: T. EL Gnaoui, H. Tilly, N. Mounier, C. Gisselbrecht, C. Sebban, O. Casasnovas, R. Delarue, T. Petrella, D. Canioni, C. Haioun
Journal: Journal of Clinical Oncology (2010)

8011 Background: We conducted a multi-center phase II trial using R-GemOx: R (375mg/m2, d1), Gem (1,000 mg/m2,d2) and Ox (100 mg/m2, d2) to confirm the efficacy and safety of an outpatient salvage regimen for patients (pts) with DLBCL non eligible for HDT(El gnaoui. Ann Oncol 2007). Methods: The primary objective was to determine the overall response rate (ORR) after 4 cycles given every 2 weeks. Patients were planned to receive 8 cycles if at least in PR after 4 cycles. Between August 2003 and January 2009, 49 pts with refractory (n=6)/relapsing (n=43, including early relapse < 12m: 16 pts) were treated in 7 institutions. Median age was 65 y (range: 41-77). Prior treatment included rituximab in 31 (63%) and HDT in 17 (35%). IPI at enrolment was > 2 in 34 pts (71%). Median delay between last treatment and R-GemOx was 14 months (m). 36 pts were in first relapse and 7 in second. Results: Sequential analyses were performed every five pts using triangular test. After 4 cycles, responses were: CR/CRu: 21 (44%), PR: 8 (17%) resulting in an ORR of 61%. At the end of treatment, 18 pts achieved CR/CRu, 4 remained in PR and 7 pts progressed. Factors significantly affecting response rate were: refractory/ early relapse 18% vs 54% (p=0.001) and prior exposure to rituximab 23% vs 65% (p=0.004). With a median follow-up of 41 m, 3y-PFS and OS were 20% (CI 10-33%) and 28% (CI 16-42%), respectively. 3y-PFS was affected by prior treatment with rituximab, 11% vs 35% (p=0.03) and refractory/early relapse 14% vs 26% (p=0.02). Grade 3-4 neutropenia and thrombocytopenia were reported for 73% and 44% of the 273 cycles delivered. A grade 3-4 infection was observed in 22% of the cycles. Conclusions: The R-GemOx regimen is a safe outpatient regimen for relapsed refractory DLBCL not candidate for HDT. This regimen could be considered as a platform for new combinations with targeted treatment in order to improve PFS, especially in refractory and early relapsed pts previously treated with rituximab. No significant financial relationships to disclose.