tbuckley/cabot-search huggingface dataset:
Mantle cell lymphoma (MCL): Induction therapy with HyperCVAD/High-dose methotrexate and cytarabine (M-C) (±rituximab) improves results of autologous stem cell transplant in first remission
Authors: J. Vose, F. Loberiza, P. Bierman, G. Bociek, J. Armitage
Journal: Journal of Clinical Oncology (2006)

7511 Background: Although patients (pts) with MCL have a high response rate to standard chemotherapy, they continue to relapse with no plateau in long term disease-free survival. The use of dose intense induction therapy such as HyperCVAD (M-C) ±Rituximab(R) and high-dose therapy and stem cell may improve these results. In this analysis the outcomes of pts receiving a standard anthracycline induction therapy or HyperCVAD(M-C)(±R) then followed by a stem cell transplant in first complete (CR1) or partial remission (PR1) were compared. Methods: Between 6/91 and 11/05, 124 pts with MCL received high-dose chemotherapy and a stem cell transplant. Of these pts, 80 received an autologous stem cell transplant in CR1 (N = 47) or PR1 (N = 33). A standard anthracycline based CHOP-like (±R) induction therapy was given to 48 pts compared with 32 pts who received HyperCVAD(M-C)(±R) prior to transplant. Results: The median age of pts was 56 years (range 33–70). The male:female ratio was 33:57. Bone marrow involvement prior to conditioning was present in 52% of pts. An elevated lactic dehydrogenase (LDH) was present in 58% of pts. 65% of patients received one prior chemotherapy before coming to stem cell transplant. The median follow up of pts is 38 months (range 3–143). Progression-free survival (PFS) and overall survival (OS) are outlined in table 1 . Characteristics associated with an improved OS by multivariate analysis included receiving HyperCVAD induction (p = 0.04), transplant in CR1 (p = 0.009), ≤ 3 prior chemotherapy regimens (p = 0.02) and no B symptoms at transplant (p = 0.05). Conclusions: To improve the long term disease free survival for pts with MCL, Hyper-CVAD(M-C)(±R) induction should be given to eligible patients with autolgous stem cell transplantation in CR1. [Table: see text] No significant financial relationships to disclose.
Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): Safety and preliminary efficacy results.
Authors: Madhur Garg, Jeanette Y Lee, Lisa A. Kachnic, Paul J. Catalano, David H. Henry, Timothy Patrick Cooley, Lee Ratner, William Wachsman, David Michael Aboulafia, Al Bowen Benson, Joel Palefsky, Richard Whittington, Ronald T. Mitsuyasu, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2012)

4030 Background: Epidermal growth factor receptor (EGFR) expression and HPV infection are common in SCAC. We therefore initiated 2 phase II studies to evaluate the safety and efficacy of the EGFR inhibitor CX given concurrently with CDDP/5-FU/RT in HIV-positive (AMC045) and immunocompetent (E3205) patients with SCAC. Methods: All patients received CX (400 mg/m2 loading, then 250 mg/m2/wk IV x 6-8 wks) plus CDDP (75 mg/m2 IV q28 days x 2) and 5-FU (1000 mg/m2/day IV infusion days 1-4 q 28 days x 2) concurrently with RT (45-54 Gy) beginning with CX dose 2. Patients in E3205 also received 2 cycles of CDDP/5-FU alone prior to CX/CDDP/5-FU/RT; this was discontinued on recommendation of the NCI Anorectal Task Force after 28 patients. Both trials were powered to detect a reduction in 3-year local-regional failure (LRF) rate from 35% to 17.5% (alpha=0.10, beta=0.10), the primary end point. Other endpoints included progression free survival (PFS) and overall survival (OS). The results below include complete toxicity and preliminary efficacy data (including only the first 28 patients from E3205). Results: Expedited reporting was required for type I (any grade 5, grade 4 cardiac) or II (grade 4 RT skin, diarrhea) adverse events, with prespecified rates of &gt;5% or &gt;20%, respectively defined as unacceptable. Early stopping rules were not invoked for either trial. LRF rates data will be presented after more detailed case review is completed. Conclusions: CX plus CDDP/5-FU/RT is feasible in patients with SCAC, including patients with HIV infection. Preliminary safety and efficacy data appear encouraging, but accrual without neoadjuvant CDDP/5-FU continues in E3205, and additional followup of both study cohorts is required in order to determine whether pre-specified efficacy endpoints were met. [Table: see text]
Symptoms and management of symptoms in cancer patients who underwent acute inpatient rehabilitation
Authors: Y. Guo, B. Young, S. Hainley, J. L. Palmer, E. Bruera
Journal: Journal of Clinical Oncology (2005)

8059 Background The purpose of this study is to examine the symptoms of cancer patients who undergone our acute in-patient rehabilitation and frequency of medication prescribed for symptom-management upon discharge. Methods: 100 charts were reviewed (96 evaluable). Symptom assessments on admission were collected on all 96 patients, only 63/96 (66%) assessments were available upon discharge. The symptoms were assessed by Anderson Symptom Assessment Scale (0–10). Descriptive analysis was used for each symptom, Sign test for improvement of symptom. Results: The mean age of the 96 patients evaluated were 63 (26–87) years old. Among the multiple symptoms at admission, the most severe symptom complaints were fatigue, poor appetite and insomnia (3.4±2.6, 3.7±3.3, 3.0±3.0 respectively), followed by pain, anxiety and constipation. Upon discharge from rehabilitation, the most severe symptom complaint is still fatigue and poor appetite (2.2±2.1, 2.2±2.4). Significant improvement is noted in area of pain, fatigue, anxiety, appetite, insomnia, constipation and sense of well-being (p= 0.003, 0.002, 0.001, 0.004, 0.04, 0.001, 0.01 respectively). Upon discharge, the percentage of patients received the following prescriptions: 65/93 (70%) pain medication, 36/93 (39%) medication to improve appetite, 7/93 (8%) methylphenidate, 45/93 (48%) laxatives, 22/96 (24%) hypnotics, and 12/93 (13%) anti-depressant. The poor appetite and depression admission score positively correlated with length of hospital stay (p=0.0002 and 0.05 respectively); poor appetite also positively correlated with length of rehabilitation stay (p=0.001). Conclusion: Significant improvement of multiple symptoms was achieved during in-patient cancer rehabilitation. Anorexia severity was a predictor of hospital and rehabilitation length of stay. No significant financial relationships to disclose.
An investigational rapid RT-PCR assay for the detection of metastasis in sentinel lymph nodes shows improved performance over frozen section H&amp;E: Analysis by primary tumor characteristics
Authors: P. Blumencranz, K. B. Deck, P. W. Whitworth, P. McCue, D. S. Reintgen, P. Beitsch, A. S. Chagpar, T. B. Julian, M. Mamounas, R. Simmons
Journal: Journal of Clinical Oncology (2007)

10561 Background: In order for a RT-PCR test to accurately diagnose the metastatic status of sentinel lymph nodes the test must perform well across all primary tumor types. Methods: A prospective study was conducted at 11 clinical sites to evaluate a real- time RT-PCR assay (investigational GeneSearch™ Breast Lymph Node Assay, Veridex, LLC, Warren, NJ, USA) for the detection of sentinel lymph node metastasis in patients with invasive breast cancer. Detection limits were pre-set to detect only metastases that are clinically relevant (&gt; 0.2 mm). Tumor information such as tumor stage, size, type and other molecular characteristics were collected. RT-PCR assay was then compared against permanent section H&amp;E and IHC for final performance calculations. A total of 416 patients’ results were analyzed for overall assay performance: sensitivity 87.6% and specificity 94.2%. The assay was then evaluated within each primary tumor characteristics category. Results: Overall RT-PCR sensitivity is an improvement (p= 0.039) over that of current intra-operative methods (frozen section H&amp;E), while specificity is similar (p=0.054). For the various tumor sub-types, in a matched dataset, the RT-PCR assay has up to 35.7% (Invasive Lobular) higher sensitivity compared to frozen section H&amp;E. Conclusions: The data suggest that the RT-PCR assay performs well and has higher sensitivity than frozen section H&amp;E regardless of primary tumor characteristics and, therefore, can be used to detect metastasis for all types of invasive breast cancer. [Table: see text] No significant financial relationships to disclose.
Clinical features at presentation in pulymyalgia rheumatica (PMR): Results from a multi-centre prospective cohort study
Authors: B Dasgupta, A Hutchings, J Hollywood, C Pease, K Chakravarty, B Hazleman, B Silverman, Ernest Choy, David Scott, B Bourke, N Gendi, D Lamping
Journal: Annals of the Rheumatic Diseases (2004)
Abstract 12279: Novel and Reliable Method to Screen for Drug Cardiac Toxicity Using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hiPS-CM)
Authors: Tamer M Mohamed, Bernhard Ellinger, Vera Stankovikj, Adriana Wiesinger, Kaomei Guan, Ludwig Neyses, Delvac Oceandy, Sheraz Gul, Elizabeth J Cartwright
Journal: Circulation (2014)

Unexpected cardiotoxicity underlies high rates of attrition during drug development, posing a multi-billion dollar burden on the pharmaceutical industry. Over reliance on the use of animals and materials derived from animals in preclinical assays to predict the cardiotoxic effect of new drugs in humans has contributed to this problem. The drug responses in human cardiomyocytes compared to animal-derived primary cardiomyocytes (CM) for in vitro assays is not always the same. Here, we describe a combination of human pluripotent stem cell-derived cardiomyocytes (hiPS-CM) and high content analysis confocal microscopy as a potential solution for this major setback in drug development. Initially human skin fibroblasts were reprogrammed into human induced pluripotent stem cells (hiPSCs) by lentiviral transduction and utilization of the following combination of transcription factors: Oct3/4, Sox2, c-Myc and Klf4. The human pluripotent stem cell phenotype of the generated hIPSCs was confirmed. hiPSCs were differentiated into cardiomyocytes and the cardiac cell phenotype was confirmed by immunofluorescence and RT-PCR analysis of cardiac markers i.e. αMHC, cTNT, NKX2.5 and connexin 43. Seventeen known cardiotoxic compounds, as well as controls, were applied to the cells in 384 well format at a dose of 10μM for 48 hours. Then hiPSC-CM underwent confocal microscopy high content analysis to simultaneously evaluate the cell mitochondrial transmembrane potential (using TMRM dye), and plasma membrane permeability (using TOTO-3 dye). All known cardiotoxins showed a significant decrease in mitochondrial transmembrane potential ranging from 74% to 95% and an increase in plasma membrane permeability ranging from 67-327 fold in comparison to the controls. These results showed 100% prediction rate of cardiotoxicity of known cardiotoxins by hiPS-CM. This was compared to only 12% general cytotoxicity prediction rate when these compounds tested on A549 and ACHN cancer cell lines. In conclusion, combining two state of the art technologies 1) hiPSC-CM and 2) confocal microscopy high content analysis, we were able to provide a reliable high throughput method to assess cardiotoxicity of compounds.
Abstract P240: Iq’Mik Smokeless Tobacco Use And Cardio-Metabolic Risk Factors Among Yup’Ik Alaska Native People
Authors: Tove K Ryman, Melissa A Austin, Scarlett Hopkins, Jacques Philip, Shirley A Beresford, Beti Thompson, Kenneth E Thummel, Bert B Boyer
Journal: Circulation (2015)

Introduction:  The traditional lifestyle of Yup’ik Alaska Native people, including a diet high in marine-based foods and daily physical activity, may be cardio-protective. However iq’mik, a traditional form of smokeless tobacco used by >50% of Yup’ik adults, could increase cardio-metabolic (CM) risk.   Objective:  Our objective was to characterize the associations between iq’mik use and CM risk factors (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], blood glucose [BG], systolic blood pressure [SBP], diastolic blood pressure [DBP], heart rate [HR] and body mass index [BMI]).   Methods:  We analyzed a cross-sectional sample of Yup’ik adults (n=874). Current iq’mik use, demographic and lifestyle data were collected through interviews. Fasting blood samples were collected to measure LDL-C, HDL-C, TG and BG. SBP, DBP, HR and BMI were obtained by physical exam.  We characterized the association between current iq’mik use and continuous CM risk factor measures both unadjusted for lifestyle and adjusted for lifestyle using two approaches, adjustment for: A) measures of Yup’ik lifestyle and B) a propensity score representing the conditional probability of using iq’mik.   Findings:  Current iq’mik use was significantly associated with increased HDL-C levels and inversely associated with TG, BG, HR, and BMI (Table). However, after adjusting for lifestyle by either method, associations were attenuated, only BG remaining inversely associated with current iq’mik use (Table).   Conclusions:  Iq’mik use was associated with cardio-protective measures when not adjusted for Yup’ik lifestyle factors. After adjusting for aspects of Yup’ik lifestyle, the inverse association between iq’mik use and BG remained, raising additional research questions about physiologic mechanisms.
Phase II trial of the oral mTOR inhibitor everolimus (RAD001) for patients with relapsed or refractory lymphoma
Authors: P. B. Johnston, S. M. Ansell, J. P. Colgan, T. M. Habermann, D. J. Inwards, S. N. Markovic, I. N. Micallef, L. F. Porrata, B. R. LaPlant, S. M. Geyer, T. E. Witzig
Journal: Journal of Clinical Oncology (2007)

8055 Background: mTOR inhibition with intravenous temsirolimus (Wyeth Pharmaceuticals) has been associated with responses in mantle cell lymphoma (J Clin Oncol 23;5347, 2005) as well as other lymphomas (Blood 108 (11) 2483; 2006). This phase II study tested the oral mTOR inhibitor everolimus (RAD001, Novartis Pharmaceuticals) in three simultaneous two-stage phase II lymphoma studies - aggressive (group 1), indolent (group 2), or uncommon (group 3). The goals were to learn the toxicity profile and to assess the anti-tumor response. Planned interim analysis for groups 1 and 3 have been completed and are the subject of this report. Methods: Patients (pts) received 10 mg PO daily for each 28 day cycle (up to 12) and restaged after 2, 6, and 12 cycles. The primary endpoint is the confirmed response rate, including CR, CRu or PR. 12 pts were enrolled in stage 1 of each study. At least 1 success in 12 is required to proceed to stage 2, to a total of 37 pts. Overall, the treatment will be considered promising if 4 or more successes are observed in all 37 pts in each group. Results: The median age of the 12 pts in group 1 was 68.5 yrs (range: 53–80), with a median of 3 (range, 1–15) prior therapies. Four pts had a prior stem cell transplant (SCT). Pts completed a median of 7 (range, 1–12) cycles of therapy. 6 confirmed responses have been achieved (1 CR, 5 PR), meeting the overall criteria for promising results in this study. Common grade 3 adverse events (AEs) include thrombocytopenia (3 pts) and anemia (2 pts). For group 3, the median age was 49 yrs (range, 27–78), with a median of 7 (range, 1–13) prior therapies and 6 pts had a prior SCT. Pts have completed a median of 6.5 cycles (range, 1–11). 5 confirmed responses have been achieved (5 PR), meeting the criteria for this regimen to be considered promising. Of these 5 patients, 3 had HD, 1 T-cell NHL, and 1 had macroglobulinemia. Common grade 3 AEs include anemia (3 pts) and thrombocytopenia (2 pts). No grade 4 AEs were reported. Conclusions: Oral everolimus has activity in a spectrum of lymphomas with acceptable toxicity. The responses observed in both group 1 and group 3 met the criteria to continue accrual. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens. No significant financial relationships to disclose.
Communicating the Health Effects of Climate Change
Authors: Howard Koh
Journal: JAMA (2016)

varying preexisting health risks; behavioral health risks; and access to local, state, and federal social services, Burgard said. In addition,more studies areneeded to explorehowrecessionsaffect small andmedium-sized groups, such as families and neighborhoods, noted Burgard. Holmes expectsBrenner’s studywill beacatalyst for more research on the link between health spending and disease mortality. “It was an interesting study. People can easily understand it. I predict it will be influential, and there will bemuchmore to study in the future looking at slightly different approaches on the main idea,” Holmes said. Such research, he explained, might address the types of health care spending, causes of mortality,andpopulations—suchaspeople in certain incomebrackets, age ranges,or racial orethnicgroups—thataremostresponsiveto the protective effects of health spending.
Observer Disagreement in the Classification and Histology of Hodgkin's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L. W. Coppleson, R. M. Factor, S. B. Strum, P. W. Graff, H. Rappaport
Journal: JNCI Journal of the National Cancer Institute (1970)

Individual observers, independently evaluating the histologic aspects of the classification of Hodgkin's disease, had a level of agreement too low to be scientifically useful. Working together, however, with appropriate statistical advice and quality control, 3 observers can provide histologic data of significantly better quality for studies of this disease. In addition, the use of 3 observers increases the accuracy of classifying individual cases beyond that which could be achieved by even the most experienced observer working alone. The results of this study raise serious doubt about the validity of clinical therapeutic trials in which the diagnosis and classification of lymphoreticular neoplasms are based on single observations by pathologists of varying experience. The use of consensus findings of a panel of pathologists is recommended in the diagnosis and classification of Hodgkin's disease and in any disorder which is difficult to diagnose and to classify histologically.
Adjuvant chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) for rectal cancer patients whose postoperative yp stage 2 or 3 after preoperative chemoradiotherapy: Updated results of 3-year disease-free survival from a randomized phase II study (The ADORE).
Authors: Yong Sang Hong, Byung-Ho Nam, Kyu-Pyo Kim, Jae-Lyun Lee, Joon Oh Park, Young Suk Park, Sun Young Kim, Tae-You Kim, Jee Hyun Kim, Joong Bae Ahn, Kyung Hae Jung, Tae Won Kim
Journal: Journal of Clinical Oncology (2014)

3502 Background: To report the updated results of 5-fluorouracil (5-FU)/leucovorin (LV) (FL) with or without oxaliplatin (FOLFOX) in patients with curatively resected rectal cancer whose pathologic stages of ypII/III after preoperative chemoradiotherapy (CRT). Methods: This is a randomised phase II study accrued patients with curatively resected rectal cancer patients whose postoperative stage ypII (ypT3-4/ypN0) or III (any ypT/ypN1-2) after preoperative CRT with fluoropyrimidines alone. Patients were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (5-FU 380 mg/m2, LV 20 mg/m2 on days 1-5, every 4 weeks, 4 cycles) or FOLFOX (oxaliplatin 85 mg/m2, LV 200 mg/m2, 5-FU bolus 400 mg/m2 on day 1, 5-FU infusion 2400 mg/m2 for 46 hours, every 2 weeks, 8 cycles). Randomisation was centrally coordinated and stratified by the ypStage and participating sites. The primary endpoint was 3-year disease-free survival (DFS). Results: A total of 321 patients were randomly assigned between November 2008 and June 2012; 161 patients to FL and 160 to FOLFOX. The arms were balanced. At a median follow-up of 38.2 months (IQR, 26.4 – 50.6), 3-year DFS rate was 71.6% (95% CI, 64.6 – 78.6) in the FOLFOX arm and 62.9% (95% CI, 55.4 – 70.4) in the FL arm with a hazard ratio (HR) of 0.657 (95% CI, 0.434 – 0.994, p=0.047) by intention-to-treat analysis. After adjusting for stratification and prognostic variables, HR remained unchanged favoring FOLFOX (0.560; 95% CI 0.366 – 0.856; p=0.007) in terms of 3-year DFS. In the subgroup analysis, patients with ypStage III (HR 0.602 [0.371 – 0.977], p=0.040), ypN1b (HR 0.356 [0.132 – 0.960], p=0.041), ypN2 (HR 0.414 [0.181 – 0.946], p=0.037), and minimally regressed tumors (HR 0.395 [0.188 – 0.831, p=0.014] benefited more from FOLFOX than FL. Grade-3 or -4 adverse events were not statistically different between arms. Conclusions: Adjuvant FOLFOX demonstrated improved 3-year DFS in curatively resected rectal cancer patients whose postoperative stage of ypII/III after preoperative CRT. Clinical trial information: NCT00807911.
Osteosarcoma: relationship of response to preoperative chemotherapy and type of surgery to local recurrence.
Authors: S S Bielack, B Kempf-Bielack, K Winkler
Journal: Journal of Clinical Oncology (1996)

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.1996.14.2.683 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8636791 Osteosarcoma: relationship of response to preoperative chemotherapy and type of surgery to local recurrence. S S BielackxS S BielackSearch for articles by this author , B Kempf-BielackxB Kempf-BielackSearch for articles by this author , K WinklerxK WinklerSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.2.683 PDF "Osteosarcoma: relationship of response to preoperative chemotherapy and type of surgery to local recurrence.." Journal of Clinical Oncology, 14(2), pp. 683–684© 1996 by American Society of Clinical Oncology
Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment
Authors: Yuanyuan Li, Yu Wang, Liyun Zou, Xiangyu Tang, Yi Yang, Li Ma, Qingzhu Jia, Qingshan Ni, Siqi Liu, Lizhang Tang, Regina Lin, Elizabeth Wong, Wei Sun, Liting Wang, Quanfang Wei, Haiying Ran, Liqun Zhang, Hengning Lian, Wei Huang, Yuzhang Wu, Qi-Jing Li, Ying Wan
Journal: Immunity (2016)