tbuckley/cabot-search huggingface dataset:
Temporal trends in protocol-specified adjuvant chemotherapy dosing in obese patients with breast cancer
Authors: C. Greenman, J. J. Griggs
Journal: Journal of Clinical Oncology (2007)

11055 Purpose: Dosing of breast cancer adjuvant chemotherapy in obese women varies substantially, with up to 40% of obese women receiving reduced (compared to full weight-based) doses. Such variation indicates uncertainty about best practices. This study reports changes over time in protocol-specified dose determinations in heavy patients. Methods: The National Cancer Institute database of cooperative group trials was used to identify completed clinical trials of non-myeloablative breast cancer adjuvant chemotherapy. Dose determinations specified in each protocol were categorized into one of four groups: 1) full weight-based dosing, 2) dose reduction in heavy patients (ideal or corrected body weight used to calculate body surface area, BSA), 3) dosing in heavy patients left to physician’s discretion, or 4) no specific instructions. Results: Of 110 eligible clinical trial protocols identified, 61 (55%) were retrieved. Of the 16 protocols initiated before 1985, 15 (94%) either did not address dose determination (n = 6) or specified dose reduction (n = 9) in heavy patients. Of the 45 protocols initiated after 1985, 26 (58%) specified full weight-based dosing, 13 (29%) specified dose reductions, 4 (9%) left dosing in heavy women to the physician’s discretion, and 3 (7%) had no specific instructions for dose determinations in heavy patients. The difference in the use of full weight based doses before and after 1985 was statistically significant (p value = 0.0003, 2-sided Fisher’s exact test). One of the cooperative groups, which contributed 10 of the 45 (22%) clinical trial protocols since 1985, specifies a maximum BSA of 2.0 m 2 for cyclophosphamide and doxorubicin in all protocols. Conclusions: Over the last two decades, dose determinations in clinical trial protocols have, with the exception of one cooperative group, specified use of actual body weight. Present-day dose reductions in obese patients who are not participating in clinical trials suggest a lack of diffusion of information about optimal dosing in obesity. The continued practice of limiting the doses of cyclophosphamide and doxorubicin in patients with a BSA over 2.0 m 2 in the protocols of one cooperative group may contribute to persistent uncertainty about optimal dosing in heavy patients. No significant financial relationships to disclose.
Glucocorticoid receptors in leukemia and lymphoma.
Authors: C D Bloomfield
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.4.323 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6368761 Glucocorticoid receptors in leukemia and lymphoma. C D BloomfieldxC D BloomfieldSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.4.323 First Page PDF © 1984 by American Society of Clinical Oncology
The possibility of a human-borne with bioagent (HBBA) terrorist at foreign FOB ECPs: the perceptions of U.S. military or security personnel, a preliminary report
Authors: George Edafese Alakpa, John W. Collins Jr
Journal: Military Medical Research (2015)

The global war on terrorism has prompted an increase in the deployment of security personnel from multi-national forces on foreign lands, especially in places where known terrorist groups are based. The aim of this study was to obtain U.S. military and security personnel's perceptions of the possibility of encountering a human-borne with bioagent (HBBA) terrorist at an entry control point (ECP).This study was a mixed-method, cross-sectional, survey-based, time-limited study. A validated, five-option Likert scale questionnaire with Cronbach's alphas of 0.82 and 0.894 for Constructs 1 and 2 was distributed to over 113 respondents with combat experience.The results indicated that 92.3 % of the respondents thought it was possible for a terrorist to employ a biological agent to cause terror; 61.5 % claimed it was either possible or very possible, and 26.9 % claimed it was somewhat possible for a terrorist carrying a biological agent to successfully breach a combat Forward Operating Bases (FOB) ECP undetected. 26.9 % of the respondents agreed that "ECP soldiers are knowledgeable about bioagents (BA)", only 15.4 % responded that ECP soldiers have effective devices for detecting a BA on a terrorist at an ECP.Despite some limitations, this pre-study tends to indicate that while many U.S. military or security personnel acknowledge the possibility of an HBBA terrorist breach and the vulnerability of U.S. combat post ECPs to a BA breach, the soldiers at the ECPs lack adequate knowledge or devices to effectively detect a BA on a terrorist at an ECP.
Modulators of right ventricular apoptosis and contractility in a rat model of pulmonary hypertension
Authors: Makhosazane Zungu-Edmondson, Nataliia V. Shults, Chi-Ming Wong, Yuichiro J. Suzuki
Journal: Cardiovascular Research (2016)

Right ventricular (RV) failure is the major cause of death among patients with pulmonary arterial hypertension (PAH). However, the mechanism of RV failure has not been defined.This study examined mechanisms and consequences of RV myocyte apoptosis and fibrosis in response to PAH. Rats were injected with SU5416 (vascular endothelial growth factor inhibitor), followed by hypoxia for 3 weeks, and subsequently maintained in normoxia for 2, 5, or 14 weeks (5-, 8-, and 17-week time points after the SU5416 injection, respectively). RV systolic pressure (RVSP) was elevated to >70 mmHg at 5-week time point, and this pressure was sustained thereafter. Significant RV myocyte apoptosis and fibrosis were observed at 8- and 17-week time points. Apoptosis was associated with downregulated Bcl-xL (anti-apoptotic protein), downregulated GATA4 (transcriptional regulator of Bcl-xL), and upregulated p53 (negative regulator of GATA4 gene transcription). PAH-mediated RV apoptosis and fibrosis were attenuated in p53 knock-out rats. Despite the major loss of cardiomyocytes, RV contractility was enhanced, suggesting that the remaining myocytes can perform improved contractile functions. Improved RV contractility is associated with the increased expression of contractile and sarcoplasmic reticulum Ca(2+) uptake proteins. In contrast, the expression of calsequestrin 2 (CSQ2) was downregulated. The siRNA knockdown of CSQ2 improved RV contractility and increased the expression of contractile and Ca(2+) uptake proteins.These results suggest that RV decompensation is associated with the death of cardiomyocytes, resulting in fibrosis. However, the remaining myocytes are capable of sustaining RV contractility through the mechanism that involves CSQ2.
Abstract 86: Cardiomyocyte-Specific Ablation of Nuclear Respiratory Factor 1 in the Mouse Leads to Dysregulation of Mitochondrial Biogenesis, Apoptosis, and Heart Failure
Authors: Jeffrey E Keenan, Hagir Sulliman, Allison Ulrich, Lan Mao, Claude A Piantadosi
Journal: Circulation Research (2014)

The DNA-binding transcription factor Nuclear Respiratory Factor 1 (NRF1) regulates mitochondrial homeostasis. Its constitutive ablation in the mouse is embryonically lethal (~E3.5). This has limited our understanding of NRF1 functionality in the heart, where mitochondrial dysfunction is often a major pathogenic factor. Therefore, we generated conditional cardiomyocyte-specific NRF1 knockout mice (MYH6-mer-Cre-mer-NRF1fl/fl or NRFfl/fl) to elucidate the role of cardiac NRF1. Two weeks after NRF1 silencing, echocardiography of NRF1fl/fl hearts revealed significant reductions in left ventricular fractional shortening (Figure A). Histology demonstrated degradation of cellular structural integrity and nuclear condensation (Figure B), with a high number of TUNEL positive nuclei compared to littermate controls (MYH6-mer-Cre-mer-NRF-1wt), indicative of apoptosis (37.8% vs. 1.1%, p &lt; 0.001). The mRNA and protein levels of key mediators of mitochondrial biogenesis were evaluated by real-time RT-PCR and immunoblotting (Figure C &amp; D). Compared to littermate controls, there was down-regulation of the mitochondrial encoded NADH dehydrogenase 1, implying a reduction of functional mitochondrial mass. Key biogenesis regulators PGC1-α (protein only), Nfe2l2, and NRF2 were also reduced. In total, these data support that dysregulation of mitochondrial biogenesis after loss of NRF1 results in cardiomyocyte apoptosis and reduced left ventricular function. These findings and further delineation of the mechanisms involved should lay the foundation for the exploitation of NRF1 as a therapeutic target in heart failure.
Effects of exercise on lung inflammation in ovalbumin-sensitized and single challenged mice
Authors: Leonardo César Melo Ávila, Bárbara Fortkamp, Thayse Regina Bruggemann, Morgana Duarte da Silva, Adenir Perini, Adair Roberto Soares Santos, Deborah de Camargo Hizume
Journal: European Respiratory Journal (2012)

Background : Studies suggest that physical exercise reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during sensitization remains unclear.  Aims : To evaluate the effects of aerobic exercise in an experimental model of sensitization and single ovalbumin (OVA) challenge.  Methods : Male Swiss mice were divided into 4 groups: mice non-sensitized, non-exposed to OVA or exercise (Control, n=7); animals submitted to moderate treadmill exercise (Exercise, n=6); animals sensitized (OVA 10 µg) and single exposed to aerosolized OVA 1% (30 min) (OVA, n= 6) and animals sensitized, submitted to exercise and single exposed to OVA (OVA+Ex, n=6). 24 hours after a single OVA/saline exposure, anesthetized mice were euthanized and we performed measures of inflammatory cells from bronchoalveolar fluid (BALF), IL-4, IL-5, IL-10, IL-1ra from lung tissue by enzyme-linked immunosorbent assay and qualitative measures of IgG1 and IgE OVA-specific by Passive Cutaneous Anaphylaxis.  Results : Exercise decreased total number of cells, as well as eosinophils, neutrophils, lymphocytes and macrophages from BALF in OVA+Ex group (p Conclusion : Our results showed that aerobic physical exercise attenuated the acute lung inflammatory response induced by a single OVA-challenge in sensitized mice, suggesting immunomodulatory properties of exercise on sensitization process in asthma.
Time-Lapse and Ultrastructure Studies on the Reversal of Mitotic Arrest Induced by Vinblastine Sulfate in Earle's L Cells<xref ref-type="fn" rid="FN2">2</xref>
Authors: Awtar Krishan
Journal: JNCI Journal of the National Cancer Institute (1968)

L cells exposed to vinblastine sulfate (Velban, Lilly) for 4–24 hours did not show any spindle microtubules in association with centrioles or centromeres. More than one pair of centrioles were seen in many of these cells. Velban-induced mitotic inhibition could be readily removed when cells were washed and reincubated in fresh medium. A large number of these metaphase-blocked and multimicronucleated cells would divide within the first 4 hours after removal of the inhibition. Multipolar chromosome formations, multipolar divisions, and aberrant cytokinesis were seen in many cells released from the mitotic arrest. Aggregates of fine, amorphous, or fibrillar material and large numbers of spindle microtubules were associated with centromeres, chromosomes, and centrioles of cells recovering from the mitotic arrest.
각종 간 병변에 대한 양전자 방출 단층촬영(PET) 영상 소견 분석
Authors: 손현배 ( Hyun Bae Son ), 한철주 ( Chul Ju Han ), 김병일 ( Beung Il Kim ), 김진 ( Jin Kim ), 정숙향 ( Sook Hyang Jeong ), 김유철 ( You Cheoul Kim ), 이진오 ( Jhin Oh Lee ), 최창운 ( Chang Yun Choi ), 임상무 ( Sang Mu Im )
Journal: Clinical and Molecular Hepatology (2002)

목적: PET은 세포의 대사를 반영하는 기능적 영상기법으로서 각종 간 병변이 PET에 어떤 영상으로 나타나며, 간 종양의 진단 및 치료에 어떻게 활용될 수 있는지를 알아보고자 하였다. 대상과 방법: 간세포암 34예, 담관세포암 8예, 간 내 전이암 25예, 간 혈관종 6예, 간 농양 7예를 대상으로 PET 영상을 얻어 SUV 및 병변과 주변 조직의 SUV 비를 조사하였다. 각각의 질환에 대해 SUV, SUV 비의 평균치 및 SUV 비의 분포를 비교하였다. 결과: 담관 세포암과 전이암은 높은 SUV를 보이며, 거의 대부분 PET에서 선명하게 나타나며, 100%의 예민도를 보였다. 간세포암도 비교적 높은 SUV를 보이나 일부는 PET에서 뚜렷이 나타나지 않으며 59%의 예민도를 보였다. 혈관종은 PET에서 뚜렷이 나타난지 않는 반면, 간 농양은 뚜렷한 영상으로 나타나 100%의 예민도를 보였다. 결론: PET은 간에 발생하는 각종 병변의 진단 및 감별에 제한적이기는 하나 활용 가능성이 있으며, PET에 선명한 영상을 보이는 일부 종양에 대해 병기 판정, 재발 발견, 치료반응 평가 등의 목적에 활용될 가능성이 있는 것으로 기대된다.
Abstract PR05: Using genome-scale CRISPR-mediated loss-of-function and gain-of-function screens to analyze gene-drug interactions in cancer
Authors: Luke A. Gilbert, Marvin E. Tanenbaum, Max A. Horlbeck, Britt Adamson, Jacqueline E. Villalta, Ronald D. Vale, Martin Kampmann, Jonathan S. Weissman
Journal: Cancer Research (2015)

Abstract Drug resistance remains a pressing problem in cancer therapy. One major mode of resistance involves altered gene expression in the cancer cell. Knowing which genes can promote resistance or sensitivity to a specific cancer drug could pave the way for the development of new treatment strategies that minimize cancer drug resistance. Genome-scale loss-of-function and gain-of-function screens can be used to discover novel gene-drug interactions in cancer. RNAi and cDNA/ORF overexpression libraries have previously been used to conduct such screens, but both have drawbacks. RNAi has off-target effects, which can lead to false-positive results. cDNAs/ORFs are usually kilobases long and can be challenging to clone, verify and maintain in an overexpression library. Our recently developed CRISPR-based screening methods address these shortcomings. The technology combines different catalytically inactive Cas9 (dCas9) fusion proteins and uniquely designed short guide RNAs (sgRNA) allowing us to repress (CRISPRi) or activate (CRISPRa) the transcription of specific genes. CRISPRi uses KRAB, a repressive chromatin modifier domain, fused to dCas9. CRISPRa uses the sunCas9 system where a peptide epitope chain is fused to dCas9 and recruits multiple copies of VP64, a transcriptional activator, attached to an intracellular single-chain antibody directed against the epitope. The gene-specific region of sgRNAs is at most 25 bases, so with the help of massively parallel oligonucleotide synthesis and next-generation sequencing, we cloned and verified genome-scaled sgRNA libraries targeting 15,977 human protein-coding genes. When used for screening, we showed that CRISPRi has minimal off-target effects, one reason being that repression is highly sensitive to mismatches between sequences of the target DNA and the sgRNA. Citation Format: Luke A. Gilbert, Marvin E. Tanenbaum, Max A. Horlbeck, Britt Adamson, Jacqueline E. Villalta, Ronald D. Vale, Martin Kampmann, Jonathan S. Weissman. Using genome-scale CRISPR-mediated loss-of-function and gain-of-function screens to analyze gene-drug interactions in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR05.
Abstract 18056: High Dose Beta Blocker Use Does Not Increase the Frequency of Allergic Contrast Reaction in Coronary CT Angiogram Examinations: Results From the Advanced Cardiovascular Imaging Consortium
Authors: Anshul Aggarwal, James Smith, Neesurg Mehta, Judith Boura, Gilbert Raff, Carl Lauter, Kavitha Chinnaiyan
Journal: Circulation (2013)

Background: A higher incidence of contrast reactions have been reported in atopic patients with the use of high dose beta blockers. High dose beta blockers are often used for heart rate control during coronary CT angiography (CTA) examinations. We sought to identify allergic complications in a large, multicenter, CTA registry. Methods: Patients undergoing coronary CTA at 53 Michigan institutions from January 2009 to March 2013 and participating in the ACIC were retrospectively analyzed. Patients were separated into two categories, those with and those without history of contrast allergy. Exposure to beta blockers was noted, and allergic reactions during or after CTA examinations were noted. Allergic reactions were defined as rash/hives, respiratory complications, anaphylaxis, generalized itching, wheezing, and face swelling immediately after completion of CT coronary angiogram. Results: Overall, 60 out of 26,725 patients included in the analysis had allergic complications (0.2%). Of the patients without a history of atopy that received high dose beta blocker, 42 out of 20206 (0.2%) patients had allergic complications when compared to 9/4725 (0.2%) of patients without high dose beta blockers (p= 0.81). Of the patients with a history of allergy in the past, 8/876 (0.9%) had allergic complications as compared with 52 out of 24,931 (0.2%) of patients without a history of allergy (p=0.002). Among allergic patients who received beta blockers, there were 7 out of 779 patients (0.9%) that had allergic complications when compared to 1 out of 97 patients (1.0%) who did not receive beta blockers (p=1.00). Conclusions: The overall incidence of allergic complications in patients undergoing coronary CT angiography is very low. The incidence of allergic reactions is higher in patients with a prior history of contrast allergy. There was no impact of high dose beta blockers on the incidence of contrast allergy in atopic patients.
Delayed emesis induced by moderately emetogenic chemotherapy: Do we need to treat all patients?
Authors: E. Ballatori, F. Roila, M. Tonato, V. De Angelis, E. Riva, P. Barbian, A. Del Favero, C. Basurto, G. Ciccarese, M.A. Palladino, A.M. Mosconi, P. Anastasi, M. Picciafuoco, E. Campora, S. Chiara, F. Cognetti, V. Ferraresi, A. Fabi, R. Tonachella, S. Cirulli, R. Sabbatini, M. Federico, A. Trassoldati, V. Silingardi, Arcispedale S. Anna Ferrara, D. Donati, A. Maestri, P. Malacarne, S. Ricci, A. Antonuzzo, G. Allegrini, P.F. Conte, F. Salvati, F. Nunziati, A. Antilli, G. Catalano, S. Cascinu, F. Di Costanzo, M. Tagliaventi, A. Zaniboni, F. Meriggi, E. Cortesi, S. Ramponi, M.C. Locatelli, A. D'Antona, A. Santoro, P. Zucchinelli, E. Mantellim, G. Ferretti, C. Boni, G. Moretti, G. Scagliotti, O. Daniele, A. Lissoni, S. Tateo
Journal: Annals of Oncology (1997)
Exemestane (Exe) as primary treatment in hormonosensible early breast cancer of the elderly: Preliminary results of a phase II multicenter open Italian study
Authors: G. Mustacchi, M. Mansutti, S. Barni, M. E. Cazzaniga, A. Farris, R. Ceccherini, C. Sacco, C. Dellach
Journal: Journal of Clinical Oncology (2006)

10689 Background: In the late 90s two large phase III trials (GRETA &amp; CRC) showed that tamoxifen as sole treatment was a possible alternative to surgery in old women. Two Phase III neoadjuvant trials showed recently that letrozole is superior and anastrozole is not inferior to tamoxifen.A few phase II and a small fase III trials showed interesting results also with the steroidal inactivator exemestane. Methods: We are running a fase II open trial in early breast cancer patients aged over 70 with receptor rich tumors, treated with exemestane 25 mgs/day for 6 months before surgery. Primary endpoints are clinical response, breast conservative surgery (BCS) rate and safety. Results: Of the planned 100 patients we report preliminary results on 50 patients (mean age 81 , range 70–92) evaluable for clinical and mammographic response. 33/50 had a partial response (66%), 2/50 PD on treatment. Clinical basal mean size of tumors was 4.4 cms (4,81 in responders) and 2,67 cms the final in responders patients. Eight patients refused surgery, 12 are too early, 23/30 underwent BCS where 17 of them (74%) were unfit for BCS at basal evaluation. No remarcable exemestane related toxicity was recorded. Conclusions: As expected from published data of phase III trials in metastatic and adjuvant setting, exemestane appears to be very active also in the neoadjuvant setting. Probably there is no more need of large phase III trials in order to consider exemestane in the preoperative setting in rich receptor tumors. In old and frail patients this could also be considered as sole treatment. [Table: see text]
Early prediction of response to sorafenib treatment in patients with hepatocellular carcinoma (HCC) with 18F- fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)
Authors: E. Siemerink, N. H. Mulder, A. H. Brouwers, G. A. Hospers
Journal: Journal of Clinical Oncology (2008)

15600 Background: Recently systemic therapy has for the first time ever shown a survival advantage for patients with inoperable HCC. Although toxicity in the pivotal study seemed mild our initial experience in 6 out of 6 patients (Child Pugh A, mean age(yrs) 56,3 (42- 78))was less favorable: only half of the projected dose could be given due to grade 3/4; diarrhea, abdominal pain, hand foot skin reaction with a need to dose reduction 48 (13–113) days after start of treatment (mean days). These findings highlight the importance of early determination of response during treatment in order to limit unnecessary toxicity. Many patients with HCC do not have easily measurable disease on CT scan/ MRI due to infiltrative growth of the tumor and the background pattern of cirrhosis. Alfa-fetoprotein(AFP) elevation can also be correlated to hepatitis of cirrhosis activity and is therefore not a reliable marker. Moreover true remissions were rare in the initial studies on sorafenib. Therefore we studied the changes in 18F-FDG-PET uptake in patients with HCC during treatment with sorafenib. Methods: In six patients with inoperable HCC who were treated with sorafenib, 18F-FDG-PET (baseline and after three weeks) was added to conventional imaging (CT scan week 12) to evaluate response. Results: Two patients showed decreased uptake on 18F-FDG-PET after 3 weeks, in accordance with a partial response on CT scan in week 12. One patient showed also decreased uptake on the 18F-FDG-PET but discontinued treatment due to toxicity. One patient showed no change in 18F-FDG uptake, in accordance with stable disease on CT scan. One patient had no uptake on 18F-FDG-PET at baseline and 3 weeks. The CT scan showed stable disease. One clinical progressive patient had multiple new lesions on 18F- FDG-PET, in accordance with progressive lesions on lung X-ray/bone scan and died within 12 weeks. Conclusions: Early dynamic changes in 18F-FDG uptake in HCC patients seems predictive of response or progression to sorafenib. 18F-FDG-PET can be useful to differentiate in an early phase between responder and non-responders. No significant financial relationships to disclose.
Choice of Treatment for Graves' Disease
Journal: New England Journal of Medicine (1978)

Graves'disease is the second common endocrine disease found in the clinic, characterized by hyperthyroidism, ophthalmopathy, diffuse struma with/without dermopathy.CoMmon treatments for hyperthyroidism of Graves' disease are anti thyroid drugs, subtotal thyroidectomyorradioiodine (ml). However, reports in the medical literature present widely varying and often conflicting with regard to cure, relapse, frequency aside effects, cost, and compliance. No single form of therapy is acceptable to or suitable for all patients.   The choice of treatment should be based upon several factors, such as the age of the patients, the size of the thyroid gland, existence of complications, and other factors.    Key Words: Graves' disease - hyperthyroidism - antithyroid drugs - thyroidectomy - radioiodine
Selective Expression of mRNA Coding for the Truncated Form of Erythropoietin Receptor in Hematopoietic Cells and Its Decrease in Patients With Polycythemia Vera
Authors: Shigeru Chiba, Tokiharu Takahashi, Kenichi Takeshita, Jun Minowada, Yoshio Yazaki, Frank H. Ruddle, Hisamaru Hirai
Journal: Blood (1997)