tbuckley/cabot-search huggingface dataset:
Human Placental Aryl Hydrocarbon Hydroxylase: Studies With Fluorescence Histochemistry&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E D Gough, M C Lowe, M R Juchau
Journal: JNCI Journal of the National Cancer Institute (1975)

Tissue sections from human placentas taken at term were studied after time-sequential incubations with benzo[a]pyrene and appropriate cofactors for mixed-function oxidation. Fluorescence microscopy revealed that the enzymic reaction appeared to be most active in the syncytial trophoblast, though the fluorescence of hydroxylated metabolites also could be observed in other placental cell types. A comparison of sections from placentas with very low versus very high aryl hydrocarbon hydroxylase activities provided evidence that induction of the human placental enzyme system with pol7cyclic aromatic hydrocarbons also appeared to occur primarily in the syncytium. When considered in conjunction with previous studies on human placental aryl hydrocarbon hydroxylase, the results tended to indicate that fetal elements of the human placenta contain the necessary electron-transport components for catalysis of mixed-function oxidations of chemical carcinogens and other foreign compounds and that this hydroxtlase system is readily inducible in the same fetal cells by components present in cigarette smoke.
Informed consent in compliance studies.
Authors: K I Pritchard
Journal: Journal of Clinical Oncology (1993)

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.1993.11.12.2457 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8246035 Informed consent in compliance studies. K I PritchardxK I PritchardSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.12.2457 PDF "Informed consent in compliance studies.." Journal of Clinical Oncology, 11(12), pp. 2457–2458© 1993 by American Society of Clinical Oncology
Self-reactive IgE exacerbates interferon responses associated with autoimmunity
Authors: Jill Henault, Jeffrey M Riggs, Jodi L Karnell, Vladimir M Liarski, Jianqing Li, Lena Shirinian, Linda Xu, Kerry A Casey, Michael A Smith, Deepak B Khatry, Liat Izhak, Lorraine Clarke, Ronald Herbst, Rachel Ettinger, Michelle Petri, Marcus R Clark, Tomas Mustelin, Roland Kolbeck, Miguel A Sanjuan
Journal: Nature Immunology (2015)
99m. Tc-Rituximab as Radiotracer For Molecular Imaging In Non Hodgkin Lymphoma
Authors: Ximena Camacho, Agustina Banchero, Maria Fernanda García, Marcelo Fernández, Natalia Oddone, María Moreno, Cecilia Guillermo, Juan Pablo Gambini, Pablo Cabral, Eloísa Riva
Journal: Blood (2013)
Prevalence of osteoporosis in glioma patients on enzyme inducing anticonvulsants (EIAC) and/or glucocorticoids
Authors: L. Jones, M. L. Affronti, C. W. Bohlin, J. E. Herndon, J. A. Quinn, D. A. Reardon, J. N. Rich, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2007)

19527 Background: Glioma patients are at risk for osteoporosis and associated morbidity as a result of neurological deficits, anticonvulsants and glucocorticoid therapy. The prevalence of osteoporosis in glioma patients has not been reported. We hypothesized that the prevalence of the osteopenia (defined by bone mineral density (BMD) T-score &lt; -1) or osteoporosis (defined by T- score &lt; -2: spine; T-score &lt; - 2.5: femur) in glioma patients supports consideration of bisphosphonate treatment to prevent or reduce the severity of osteoporosis and skeletal complications. Methods: BMD was conducted on 19 eligible patients. Eligibility criteria included: (1) histologically confirmed diagnosis of a primary glioma, (2) age ≥ 18 years, (3) KPS ≥ 60%, (4) treated with valproate or an EIAC and/or on more than physiologic replacement steroid therapy, (5) creatinine &lt; 2.0 mg/dl and calculated creatinine clearance of &gt;60 ml/min, (6) bilirubin &lt; 1.5 x nl, LFTs &lt; 2.5 x nl, (7) recovery from surgery, (8) life expectancy &gt;12 wks, and (9) written informed consent. Exclusion criteria: Previously diagnosed with osteoporosis requiring oral bisphosphonates. Results: 89% were diagnosed with a glioblastoma. Mean age, 54.6 (±SD 9.4; range 35–70). 68% (13/19) were male and all were white race. 53% (10/19) had a KPS of ≥90: 42% (5/19) KPS ≥80: 5% (1/19) KPS ≥70%. AC use: 64% phenytoin; 11% valproate; 5% phenobarbital; 5% oxcarbazepine; 10% levetiracetam; and 5% none. 37% were on dexamethasone, 16% other steroids, and 47% off steroids. Mean N-telopeptide (a marker of bone turn over) was 12.6 (±SD 5.5; range 5.6–22.2). 22% of patients (4/19) had osteopenia and 16% (3/19) had osteoporosis. Conclusions: Overall 38% percent of glioma patients had evidence of osteopenia and 16% had osteoporosis. Thus, bisphosphonates should be considered to prevent skeletal complications. Subsequently, we have initiated an open-labeled Phase II trial to further determine the prevalence of osteoporosis in glioma patients and the effect of every three month prophylactic zoledronic acid on bone density. An update of the prevalence of osteoporosis in patients enrolled on this trial will be presented. No significant financial relationships to disclose.
AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer.
Authors: A. De Gramont, E. Van Cutsem, J. Tabernero, M. J. Moore, D. Cunningham, F. Rivera, S. Im, M. Makrutzki, A. Shang, P. M. Hoff
Journal: Journal of Clinical Oncology (2011)

362 Background: Bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has demonstrated clinical efficacy in combination with 5-FU-based regimens in patients with metastatic colorectal cancer. The therapeutic impact of concurrent BEV with either FOLFOX4 or XELOX chemotherapy in the adjuvant setting was evaluated in this international, controlled phase III trial. Methods: Eligible patients had high-risk stage II or stage III colon cancer and had undergone surgical resection. Patients were randomly assigned to one of three treatment groups and stratified by geographic region and tumor stage: Arm A: FOLFOX4 on weeks 1–24; Arm B: FOLFOX4 + BEV on weeks 1–24, then BEV alone on weeks 25–48; Arm C: XELOX + BEV on weeks 1–24, then BEV alone on weeks 25–48. The primary endpoint was disease-free survival (DFS) for patients with stage III colon cancer; secondary endpoints included overall survival (OS), and safety. DFS/OS follow-up assessments were performed every 6 months after randomization for 4 years, then annually until recurrence or death. Results: 3,451 (2,867 stage III) patients were enrolled between December 2004 and June 2007; median age was 58–59 years. Median duration of follow-up was 48 months (range 0–66 months). BEV did not prolong DFS or OS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer based on the final efficacy analysis conducted in September 2010. Efficacy results favored the chemotherapy-alone control arm. Numerically more relapses and deaths occurred in both the BEV arms compared to control. The observed adverse events were consistent with those previously reported in pivotal trials of BEV across tumor types for approved indications. Conclusions: The primary endpoint of the AVANT study was not met. BEV does not prolong DFS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer. The safety profile of BEV was consistent with prior study results. [Table: see text]
Unmanipulated HLA Haploidentical Bone Marrow Transplantation Combined With PBSC With The Options Of Donor Virus Specific CTLs and Mesenchymal Stem Cells Infusion
Authors: Yoshiyuki Takahashi, Nozomu Kawashima, Atsushi Narita, Hirotoshi Sakaguchi, Hideki Muramatsu, Asahito Hama, Seiji Kojima
Journal: Blood (2013)
STUDIES ON VITAL STAINING
Authors: H. P. Smith
Journal: The Journal of Experimental Medicine (1930)

When large amounts of brilliant vital red are injected into the blood stream of dogs, the dye is gradually removed from circulation, and most of it is deposited in numerous phagocytic cells which are scattered throughout various organs and tissues. The dye occurs largely in the form of tiny red granules crowded together in the cytoplasm of these cells. If Niagara sky blue, a closely related dyestuff, is injected, it too is taken up and stored in these same cells. It is shown that the presence of red dye in the tissues does not inhibit the cells from taking up the blue one. The normal ability of the phagocytes to take up Niagara sky blue is observed also when this dye is injected simultaneously with brilliant vital red. This normal response toward the blue dye is seen even though the phagocytes are busied at the same time in the process of engulfing and storing the red dye. These experiments show that it is difficult if not impossible to "block" the cells with one dye so that their ability to take up another is even slightly impaired. The two dyes employed in these studies are shown to be particularly suitable for experiments of the sort here reported.
Correlation between time to prostate cancer metastasis and overall survival after androgen-deprivation therapy initiation.
Authors: Loana Bueno Valenca, Lillian Werner, Wanling Xie, Mari Nakabayashi, Philip W. Kantoff, Mark M Pomerantz
Journal: Journal of Clinical Oncology (2015)

250 Background: Currently,overall survival (OS) is used to determine treatment efficacy in trials for advanced prostate cancer (PC). Reliable intermediate endpoints could hasten drug development efforts. We therefore sought to determine the association between an intermediate endpoint—time to metastasis (TTM)—and OS in PC patients receiving androgen deprivation therapy (ADT) for biochemical recurrence (BCR). Methods: The Dana-Farber PC database identified 415 patients who received ADT for non-metastatic BCR with median 6.4 years follow-up. Associations between TTM and OS were measured from (i) time of ADT initiation (n=398) and (ii) time of castration-resistance (n=247) using a non-parametric Kendall tau rank correlation for bivariate time to event outcomes. A Cox regression model was used to assess the association of development of metastasis and OS for landmark timepoints. Results: Among 398 subjects analyzed from start of ADT, 180 (45%) developed metastases with median TTM 6.25 years. A total of 152 (38%) died, with a median OS of 8.5 years. For men developing metastases within five years of ADT initiation, hazard ratio (HR) for mortality was 7.42 (p&lt;0.0001, 95% CI 4.18-13.17). Among 247 subjects assessed from time of castration resistant PC (CRPC), 172 (70%) developed metastases with a median TTM 2.6 years. In this subgroup, 140 (56%) patients died with median OS 5.25 years. For men developing metastases within three years of developing castration-resistance, HR for mortality was 5.25 (p&lt;0.0001, 95% CI 3.20-8.61). Overall, correlation between TTM and OS from ADT initiation and OS was 0.25 (P&lt;0.0001, 95% CI 0.20-0.29). Correlation between TTM and OS from CRPC was 0.32 (P&lt;0.0001, 95% CI 0.25-0.37). Conclusions: TTM was significantly correlated with OS in PC patients treated with ADT for BCR. Prospective data in a large validation cohort will help determine whether TTM is suitably predictive of OS to serve as a primary endpoint in clinical trials.
High copy number of highly similar mariner-like transposons in planarian (Platyhelminthe): evidence for a trans-phyla horizontal transfer.
Authors: J Garcia-Fernàndez, J R Bayascas-Ramírez, G Marfany, A M Muñoz-Mármol, A Casali, J Baguñà, E Saló
Journal: Molecular Biology and Evolution (1995)

Several DNA sequences similar to the mariner element were isolated and characterized in the platyhelminthe Dugesia (Girardia) tigrina. They were 1,288 bp long, flanked by two 32 bp-inverted repeats, and contained a single 339 amino acid open-reading frame (ORF) encoding the transposase. The number of copies of this element is approximately 8,000 per haploid genome, constituting a member of the middle-repetitive DNA of Dugesia tigrina. Sequence analysis of several elements showed a high percentage of conservation between the different copies. Most of them presented an intact ORF and the standard signals of actively expressed genes, which suggests that some of them are or have recently been functional transposons. The high degree of similarity shared with other mariner elements from some arthropods, together with the fact that this element is undetectable in other planarian species, strongly suggests a case of horizontal transfer between these two distant phyla.
Management of Diabetes in Long-term Care and Skilled Nursing Facilities: A Position Statement of the American Diabetes Association
Authors: Medha N. Munshi, Hermes Florez, Elbert S. Huang, Rita R. Kalyani, Maria Mupanomunda, Naushira Pandya, Carrie S. Swift, Tracey H. Taveira, Linda B. Haas
Journal: Diabetes Care (2016)

Diabetes is more common in older adults, has a high prevalence in long-term care (LTC) facilities, and is associated with significant disease burden and higher cost. The heterogeneity of this population with regard to comorbidities and overall health status is critical to establishing personalized goals and treatments for diabetes. The risk of hypoglycemia is the most important factor in determining glycemic goals due to the catastrophic consequences in this population. Simplified treatment regimens are preferred, and the sole use of sliding scale insulin (SSI) should be avoided. This position statement provides a classification system for older adults in LTC settings, describes how diabetes goals and management should be tailored based on comorbidities, delineates key issues to consider when using glucose-lowering agents in this population, and provides recommendations on how to replace SSI in LTC facilities. As these patients transition from one setting to another, or from one provider to another, their risk for adverse events increases. Strategies are presented to reduce these risks and ensure safe transitions. This article addresses diabetes management at end of life and in those receiving palliative and hospice care. The integration of diabetes management into LTC facilities is important and requires an interprofessional team approach. To facilitate this approach, acceptance by administrative personnel is needed, as are protocols and possibly system changes. It is important for clinicians to understand the characteristics, challenges, and barriers related to the older population living in LTC facilities as well as the proper functioning of the facilities themselves. Once these challenges are identified, individualized approaches can be designed to improve diabetes management while lowering the risk of hypoglycemia and ultimately improving quality of life.
The relationship between health utility, quality of life, and symptom scores in Canadian patients with esophageal cancer.
Authors: Mark Doherty, Hiten Naik, Lawson Eng, Devalben Patel, Qin Quinn Kong, Wei Xu, Catherine Brown, Osvaldo Espin-Garcia, Ashlee Vennettilli, Daniel John Renouf, Olusola Olusesan Faluyi, Jennifer J. Knox, Helen Mackay, Rebecca Wong, Doris Howell, Nicole Mittmann, Gail Elizabeth Darling, David Cella, Geoffrey Liu
Journal: Journal of Clinical Oncology (2015)

149 Background: Health Utility scores (HUS) are an increasingly important tool in helping to determine the cost-effectiveness of therapies worldwide. The EQ-5D is a validated HUS questionnaire, with reference data in numerous populations. Previously, HUS in esophageal cancer (EC) were based on limited datasets, and the relationship between HUS and either quality of life (QOL, through the validated FACT-E) or esophageal-specific symptoms such as dysphagia, has not been studied. Methods: This cross-sectional survey of EC patients at Princess Margaret Cancer Centre (2012-2014) assessed EQ-5D, FACT-E, a Visual Analog Scale (VAS), patient reported performance status (PRO-ECOG), and dysphagia scoring. EQ-5D scores were converted to HUS using Canadian references. Correlation analyses were performed between HUS and global FACT-E scores, global dysphagia scores, and specific esophageal symptom scores included in FACT-E. Results: Of 198 patients, median age was 67 (range 32-93) years, 76% were male, with localized (LD stage 1, 6%), regional (RD, stage II-IVA, 62%), and metastatic (MD, stage IVB, 27%) disease. Mean + SEM EQ-5D HUS was 0.80+0.01 (all patients), 0.90+0.05 (LD), 0.82+0.01 (RD), and 0.73+0.03 (MD) [p=0.03]. Mean FACT-E total score was 130, mean total FACT-G score was 80, and mean ECS score was 49. There was a strong correlation between FACT-E total scores and EQ-5D HUS (r=0.73, p&lt;0.001), and mild-to-moderate correlation between FACT-E dysphagia questions and HUS (r= 0.28-0.37; p&lt;0.001, each comparison) and between the odynophagia question and HUS (r=0.28, p&lt;0.001). A moderate correlation was observed between a non-FACT-E based global swallow score and HUS (r=0.48, p&lt;0.001). Conclusions: In this large cross-sectional study of EC patients, stage, QOL, and esophageal-specific symptoms were all associated with HUS. Additional results will be presented on the relationship of VAS, PRO-ECOG and specific FACT-E domains, with HUS and changes in questionnaire scores over time, as well as stage-specific EC reference HUS using UK and USA references. This research enhances our understanding of the factors driving EQ5D HUS in EC, thereby validating its potential usefulness in economic analyses.
Phase I study of bavituximab, a novel anti-phosphatidylserine monoclonal antibody in patients with advanced refractory cancer: Preliminary results
Authors: N. K. Ibrahim, L. Wong, L. Rosen, J. Shan
Journal: Journal of Clinical Oncology (2009)

1080 Background: Aminophospholipid are normally expressed on damaged or apoptotic cells, as well as on the intravascular surface of EC of vessels feeding the tumor as a result of the tumor microenvironment (e.g., hypoxia, reactive oxygen species). Bavituximab (B), a novel monoclonal antibody against PS, has demonstrated preclinical anti-tumor activity by eliciting both innate and adaptive immune responses specific to tumor vasculature. Here we report preliminary results of the phase I study in patients (pts) with advanced solid tumors. Methods: This is a phase I, dose escalation, safety, tolerability and pharmacokinetic (PK) study, as well as to define DLT, MTD and/or maximum effective dose (MED) in pts with advanced refractory cancers. Planned cohorts of 6 pts, each were to receive 0.1, 0.3, 1 or 3 mg/kg. Escalation was permitted if mean cohort Cmax ≤ 65 mcg/mL and dose limiting toxicities (DLT) was observed in ≤ 1 of 6 pts. No premedication was planned or needed. DLT was defined as ≥ grade 3 drug-related adverse events (AE), ≥ grade 2 PT, or ≥ grade 3 aPTT. B was given as a 90 minute IV infusion (on days 0, 28, 35, 42 for the first two dose cohorts and 0, 7, 14, 21 for the third- and fourth-dose cohorts. Although not a study endpoint, tumor response was collected at day 56. Results: Data are available for the first 20 pts enrolled (10 breast, 3 colorectal, 2 pancreatic, 1 each of hepatocellular carcinoma, head and neck, melanoma, mesothelioma, and prostate cancer). Cohorts by dose: 0.1 mg/kg (8 pts), 0.3 mg/kg (6pts), and 1 mg/kg (6pts). Median age was 59 years and 70% of pts were females. (Q: see attached Excel file). No DLTs or drug-related severe AEs were reported. Common drug-related AEs were fatigue (7pts), nausea (6 pts), dry skin (3 pts), constipation (2 pts) and dyspnea (2 pts). All AEs were grade 1 or 2 and no dose relationship was observed. PK was dose proportional with mean serum Cmax of 2.3, 5.2 and 16.6 mcg/mL for the 0.1, 0.3 and 1 mg/kg groups, respectively. No accumulation of B was seen after multiple weekly dosing. Conclusions: Single agent bavituximab is well tolerated to date, with a predictable PK profile. Accrual of the last planned cohort is underway. MTD has not been reached. Final results will be available for presentation at the time of the Meeting. [Table: see text]
Phase I and Pharmacokinetic Study of Irinotecan and Docetaxel in Patients With Advanced Solid Tumors: Preliminary Evidence of Clinical Activity
Authors: Alex A. Adjei, Cheri E. Klein, Helen Kastrissios, Richard M. Goldberg, Steven R. Alberts, Henry C. Pitot, Jeff A. Sloan, Joel M. Reid, Lorelei J. Hanson, Pamela Atherton, Joseph Rubin, Charles Erlichman
Journal: Journal of Clinical Oncology (2000)

PURPOSE: The goals of this study were to determine the maximum-tolerated dose and describe the toxicities of the combination of irinotecan and docetaxel administered every 3 weeks to patients with advanced malignancies and, also, to evaluate the effect of irinotecan on the disposition of docetaxel and describe preliminary evidence of antitumor activity. PATIENTS AND METHODS: Eighteen patients received 85 courses (median, two courses; range, one to 15 courses) of treatment with irinotecan, administered over 90 minutes by intravenous infusion, followed by docetaxel, administered over 60 minutes by intravenous infusion. Four escalating dose levels of irinotecan/docetaxel (160/50 mg/m 2 , 160/65 mg/m 2 , 200/65 mg/m 2 , and 200/75 mg/m 2 ) were studied. Pharmacokinetic analyses were performed to evaluate the effect of irinotecan on the disposition of docetaxel. RESULTS: The most common and dose-limiting toxicity was myelosuppression, which consisted of neutropenia that was severe (National Cancer Institute common toxicity criteria [NCI CTC] grade 4) but brief (&lt; 5 days) in 11 patients, with three episodes of febrile neutropenia. Nonhematologic toxicities of anorexia, nausea, and stomatitis were mild to moderate (NCI CTC grades 1 and 2), but there was one incidence each of both CTC grade 3 anorexia and nausea. All patients had total alopecia. Diarrhea was dose-dependent and severe in four patients who failed to take adequate antidiarrhea therapy. Five out of 16 assessable patients, one with cholangiocarcinoma, one with leiomyosarcoma, and three with non–small-cell lung cancer, achieved partial remissions. CONCLUSION: The combination of irinotecan and docetaxel causes significant reversible myelosuppression, which was dose limiting but led to no serious sequelae. There was no evidence of a clinically significant interaction using these two agents in this sequence. The combination showed antitumor activity at all the dose levels tested and should be further studied in a number of tumor types. The recommended phase II dose on this schedule is irinotecan 160 mg/m 2 and docetaxel 65 mg/m 2 .
연구논문 : 응급 간이식을 받은 전격성 A형간염 환자의 임상 양상: 다른 원인에 의한 급성 간부전 환자와의 비교
Authors: 김진동 ( Jin Dong Kim ), 최종영 ( Jong Young Choi ), 박정화 ( Chung Hwa Park ), 송명준 ( Myeong Jun Song ), 장정원 ( Jeong Won Jang ), 배시현 ( Si Hyun Bae ), 윤승규 ( Seung Kew Yoon ), 이영석 ( Young Sok Lee ), 유영경 ( Young Kyoung You ), 김동구 ( Dong Goo Kim )
Journal: Clinical and Molecular Hepatology (2010)

목적: 최근 A형간염에 따른 전격성 간부전이 증가하고, 이에 따른 응급 간이식이 많이 시행되고 있다. 이 연구에서 전격성 A형간염으로 간이식을 시행받은 환자의 임상적 특징을 분석하고자 하였다. 대상 및 방법: 2007년 12월부터 2009년 5월까지 본 이식센터에서 기저 간질환 없이 IgM anti-HAV 항체 양성으로 간이식을 시행받은 환자 11명의 임상자료를 같은 분기에 다른 원인의 급성 간부전으로 이식을 받은 환자 10명의 자료와 후향적으로 비교하였다. 결과: A형간염에 의한 간부전군(HAV군)의 연령은 중앙값이 34세(범위: 15~43)였고, 남자가 3명(27.3%)이었다. HAV군에서 다른 원인의간부전군(non-HAV군)보다 헤모글로빈, AST, ALT, 레아티닌 수치가 높았고(각각 P=0.005, 0.001, 0.001, 0.010), 빌리루빈 수치는 낮았다(P=0.003). HAV군에서 임상증상을 처음 자각한 시점부터 간성뇌증의 발현까지의 기간은 중앙값이 5일(범위: 4~13)로 임상 경과가 빠르게 진행했다(P<0.001). HAV 군에서 간성뇌증의 진행은 실험실검사 소견 및 기존 예후예측모델의 점수와 연관성이 낮았고, 기존의 간이식 기준과 부합하는 경우도 적었다. 결론: A형간염에 의한 급성 간부전 환자의 임상 양상은 빠르게 진행하며, 실험실검사 소견이나 기존의 예후예측모델은 A형간염 환자에서 간이식 대상자를 선정하는 기준으로 충분하지 않다.
Pre-Clinical and Clinical Evaluation of Azd9291, a Mutation-Specific Inhibitor, in Treatment-Naïve Egfr Mutated Nsclc
Authors: S.S. Ramalingam, Y. Ohe, N. Nogami, J.C. Yang, C. Eberlein, S. Ashton, M. Mellor, P. Spitzler, C. Meador, E. Ichihara, D. Cross, W. Pao, P. Ballard, G. Hughes, M. Cantarini, P. Frewer, S. Ghiorghiu, P.A. Janne
Journal: Annals of Oncology (2014)