tbuckley/cabot-search huggingface dataset:
Interferon-based chemoradiation as primary therapy for locally advanced pancreatic cancer: A phase II trial
Authors: V. J. Picozzi, N. Boone-Hill, L. W. Traverso, R. A. Kozarek
Journal: Journal of Clinical Oncology (2007)

15082 Background: Locally advanced pancreas cancer (LAPD) is a therapeutic challenge for clinicians worldwide. Chemoradiation and chemotherapy-only approaches are used, typically producing overall survival (OS) of only 9–14 months (mo). In 1995, we developed a unique chemoradiation method using cisplatin (C), 5-FU (F), and alpha-interferon (IFN) , followed by post-chemoradiation (F). As adjuvant therapy to resected pancreas cancer; this method has produced 5-yr OS of 40%-50% in our institution.We report here a phase II trial assessing the efficacy of this regimen in LAPD. Methods: Patients with LAPD ( non-laparascopy-staged), ECOG performance score 0–1, were treated with XRT 5000cGy/25 fractions simultaneous with (C) 30mg/m2 d 1,8,15,22,29, (F) 200mg/m2 IVCI d 1–35, and (IFN) 3million U SQ qod d 1–35 .(F) 200mg/m2 IVCI was given for 2 additional 6 week cycles (weeks 9–14 and 17–22) . Therapy post- progression was given at the discretion of the treating physician. Results: From 7/1995 and 7/2002, 20 patients(pts) (median age 62) were accrued. 19/20 pts (95%) completed &gt;95% of specified XRT dose; 17/20 pts (85%) received &gt;80% of specified chemotherapy doses during XRT. 12/20 pts (60%) completed &gt;80% of specified (F) post chemoradiation. 10/20 pts (50%) experienced grade 3 toxicity during chemoradiation, and 10/20 pts (50%) required hospitalization including 4-GI symptoms (e.g.diarrhea/dehydration), 2-GI bleeding, 2-fever, 1-hyponatremia and 1-anorexia. No grade 4 toxicities and no toxic deaths occurred. All 20 pts have now expired. Initial site of disease progression was liver 8 pts, abdominal cavity 4 pts, local 4 pts, unknown 4 pts. Median time to progression was 7 mo; median OS was 12.5 mo (range 3–51 mo). 1-and 2-yr OS were 55% and 20%, respectively. 7/20 pts. received gemcitabine-based regimens following tumor progression; median OS of these pts was 17 mo. Conclusions: 1) The IFN-based chemoradiation described above is moderately severe in toxicity, but can be successfully applied to LAPD. 2) This chemoradiation method may be a sucessful platform for the treatment of LAPD with gemcitabine-based chemotherapy. Studies investigating this approach are presently underway at our institution. No significant financial relationships to disclose.
Plaque Compositional Syntax Score
Authors: Salvatore Brugaletta, Michael Magro, Cihan Simsek, Jung He Heo, Sanneke de Boer, Jurgen Ligthart, Karen Witberg, Vasim Farooq, Robert-Jan van Geuns, Carl Schultz, Nicolas van Mieghem, Evelyn Regar, Felix Zijlstra, Henricus J. Duckers, Peter de Jaegere, James E. Muller, Antonius F. van der Steen, Eric Boersma, Hector M. Garcia-Garcia, Patrick W. Serruys
Journal: JACC. Cardiovascular imaging (2012)
The Need to Target Mucosa‐Associated Lymphoid Tissue for Preventing Lymphoma in Rheumatoid Factor–Positive Patients With Sjögren's Syndrome: Comment on the Article by Nocturne et al
Authors: Luca Quartuccio, Chiara Baldini, Stefano Bombardieri, Roberta Priori, Guido Valesini, Elena Bartoloni, Alessia Alunno, Roberto Gerli, Francesco Carubbi, Roberto Giacomelli, Salvatore De Vita
Journal: Arthritis & Rheumatology (2016)
To (ss) block or better block?
Authors: M. J Brown
Journal: BMJ (1995)

Scarcely a week now passes without a new receptor subtype being described on which either endogenous neurotransmitters or hormones might act, usually as agonists, and which are rapidly proposed as novel targets for drugs, usually as antagonists. It is therefore ironic, but instructive, to recognise the debate that still stirs among doctors and pharmacologists over the relative merits of β1 selective and non-selective β blockade after more than 20 years' use in angina and hypertension.

The most recent airing of the debate concerned the paradoxical pressor response to non-selective β blockade.1 2 In the absence of β blockade, acute rises in circulating adrenaline concentrations hardly affect mean blood pressure because of opposing actions on systolic and diastolic blood pressure. The rise in systolic blood pressure is due mainly to vasoconstriction mediated by (α) adrenoceptors, and this is unopposed when a non-selective β blocker like propranololprevents the vasodilatation mediated by β2 adrenoreceptors. But two obstacles exist to concluding that selective β1 blockade must automatically be preferable.

Firstly, it is necessary to appreciate that the endocrine secretion …
Efficacy of neoadjuvant bevacizumab (Av), capecitabine (X), and docetaxel (T) for invasive breast cancer (BC): Phase II result
Authors: R. Greil, M. Moik, R. Reitsamer, S. Ressler, M. Stoll, K. Namberger, C. Menzel, B. Mlineritsch
Journal: Journal of Clinical Oncology (2008)

14575 Background: In metastatic BC, Av significantly improves patient (pt) outcomes when added to paclitaxel and has been evaluated in a large, phase III trial in combination with T (AVADO). Adding X to T significantly improves overall survival and the XTAv triplet combination is highly active first-line for metastatic BC. To evaluate XTAv in early BC, we initiated a pilot, phase II study in pts scheduled to receive neoadjuvant chemotherapy. Methods: Pts with invasive HER2-negative T2–4c >2 cm, N0–3, M0 BC and no prior systemic therapy received 21-day cycles of Av 15 mg/kg (30–90-minute IV infusion, d1×5 cycles) plus T 75 mg/m2 (d1×6 cycles) plus X (950 mg/m2 bid 14d on/7d off×6 cycles). Pts underwent surgery 2–4 weeks after completing XTAv, followed by radiotherapy, chemotherapy, and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumor in the final surgical sample (T0 or DCIS). Secondary endpoints included clinical response rate (RR), breast-conserving surgery (BCS) rate, and safety. Results: Baseline characteristics (n=18) were: median age 48 years (range 34–69); T4a (6%), T3 (39%), T2 (56%); ER+ (67%); PR+ (61%). Most pts (72%) received all 6 cycles. BCS was possible in 14 pts (78%; 95% CI: 52–94); 2 additional pts (11%) had BCS followed later by mastectomy and 2 pts (11%) underwent modified radical mastectomy. Sentinel lymph nodes were negative in 10 (67%) of 15 pts undergoing sentinel biopsy. pCR rate was 22% (95% CI: 6–48). Clinical RR was 83%. T stage was T3 (17%), T2 (11%), T1 (50%), CIS (6%), T0 (17%). XTAv was well tolerated, with no unexpected toxicities. Conclusions: The 22% pCR rate suggests that the activity of XT in HER2-negative BC can be increased by adding Av. Further evaluation of this regimen in early BC is recommended. No significant financial relationships to disclose.
Monomethylfumarate (MMF), a Novel Inducer Of Fetal Hemoglobin In Human Erythroid Progenitors and Retinal Pigment Epithelial Cells
Authors: Levi Makala, Wanwisa Promsote, Biaoru Li, Vadivel Ganapathy, Martin Pamela, Betty S. Pace
Journal: Blood (2013)
Challenging Cases and Diagnostic Dilemmas
Authors: Konstanze Spieth, Jörg Risse, Roland Kaufmann, Jens Gille
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.15.3349 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12149310 Challenging Cases and Diagnostic Dilemmas Case 3. Positron Emission Tomography Scan Mimicking Lymph Node Metastases in a High-Risk Melanoma Patient Konstanze SpiethxKonstanze SpiethSearch for articles by this author , Jörg RissexJörg RisseSearch for articles by this author , Roland KaufmannxRoland KaufmannSearch for articles by this author , Jens GillexJens GilleSearch for articles by this author Show More Zentrum der Dermatologie, Zentrum der Radiologie, Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany https://doi.org/10.1200/JCO.2002.20.15.3349 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Phase I Clinical and Pharmacokinetic Study of Oral S-1 in Patients With Advanced Solid Tumors
Authors: Cees J. van Groeningen, Godefridus J. Peters, Jan H. Schornagel, Helen Gall, Paul Noordhuis, Martin J. de Vries, Sue L. Turner, Martha S. Swart, Herbert M. Pinedo, Axel R. Hanauske, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To investigate the side effects, determine the maximum-tolerated dose (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. PATIENTS AND METHODS: Patients with advanced solid tumors received S-1 bid for 28 days, followed by 1 week of rest. 5-FU pharmacokinetics were investigated after a single initial dose of S-1 during the first 24 hours and weekly thereafter. RESULTS: Twenty-eight patients received S-1 at the four consecutive dose levels of 25, 45, 35, and 40 mg/m 2 . The MTD was initially found at 45 mg/m 2 , with diarrhea as the dose-limiting toxicity (DLT). Diarrhea was also the DLT at the dose of 40 mg/m 2 , which was the MTD for patients exposed to extensive prior chemotherapy. Other toxicities were generally mild. Two patients had a reduction of more than 50% in tumor dimension. Plasma pharmacokinetics of 5-FU were linear; at the highest S-1 dose level, 5-FU plasma peak concentrations reached 1 to 2 μmol/L, and the half-life of 5-FU was 3 to 4 hours. A statistically significant relationship was observed between the severity of diarrhea and pharmacokinetic parameters of 5-FU. CONCLUSION: The recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed patients is 40 mg/m 2 bid on 28 consecutive days, every 5 weeks. In heavily pretreated patients, the recommended dose is 35 mg/m 2 bid. Phase II trials are warranted in tumors known to be responsive to 5-FU treatment.
Optimal assessment of treatment benefit with targeted agents for hepatocellular carcinoma (HCC): An analysis of brivanib phase II data.
Authors: R. S. Finn, J. Raoul, D. Manekas, C. Baudelet, I. B. Walters
Journal: Journal of Clinical Oncology (2010)

4096 Background: Traditional oncology imaging criteria for response and progression have fallen short in assessing treatment benefit in hepatocellular carcinoma (HCC). New approaches that consider cytostatic effects of targeted therapies have been proposed in publications and incorporated in societal guidelines. Recent AASLD guidelines recommend assessment of tumor response in HCC using new modified RECIST (mRECIST) criteria to evaluate not only tumor size, but tumor viability. They also propose specific criteria for progression that take into account changes in the underlying liver. Alpha-fetoprotein (AFP) is considered an indicator of tumor activity in HCC and AFP responses have correlated with overall survival following chemotherapy treatment. Methods: Using data from a phase II study of brivanib, a dual selective inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling, we evaluated 101 advanced HCC patients (pts) who had received brivanib 800 mg/d as monotherapy. Pts were assessed by an independent committee using modified WHO (mWHO) and mRECIST criteria, with AFP values measured at each assessment. All 3 criteria were compared with outcomes to evaluate their utility. Results: Confirmed responses were seen in 5/101 pts (5 PRs) with mWHO and in 19/101 (5 CRs + 14 PRs) with mRECIST. Disease control (CR + PR + SD) was noted in 45/101 pts with mWHO and in 76/101 with mRECIST. Thirty-one pts with PD by mWHO had evidence of disease stabilization or response by mRECIST, and may have been discontinued too early from treatment. Time to progression using mRECIST was substantially longer vs mWHO and better approximated overall survival. Pts without disease stabilization by mRECIST had very short survival. All pts with elevated baseline AFP and a confirmed response by mRECIST had ≥ 40% reduction in AFP. Conclusions: In this analysis, mRECIST appears to more accurately reflect disease stabilization and progression. AFP monitoring may add additional information for pts with AFP-expressing tumors. This is one of the first studies of targeted agents that relates the use of mRECIST and AFP to response and supports the evaluation of these criteria in future HCC studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bayer, Bristol-Myers Squibb, Novartis, Taiho Pharmaceutical Bristol-Myers Squibb Bayer, Bristol-Myers Squibb Bristol-Myers Squibb
Ligand-targeted theranostic nanomedicines against cancer
Authors: Virginia J. Yao, Sara D'Angelo, Kimberly S. Butler, Christophe Theron, Tracey L. Smith, Serena Marchiò, Juri G. Gelovani, Richard L. Sidman, Andrey S. Dobroff, C. Jeffrey Brinker, Andrew R.M. Bradbury, Wadih Arap, Renata Pasqualini
Journal: Journal of Controlled Release (2016)

Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentially overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. The modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.
Abstract 12271: Stabilizing Effect of Metoprolol on Cholesterol Crystallization and Vulnerable Plaque's
Authors: Abrar R Sayeed, Fatima Muslehuddin, Mojdeh Nasiriahmadabadi, Ehtesham R Sayeed, Ruiping Huang, George S Abela
Journal: Circulation (2012)

Introduction: Cardio-protective effects of B- Blockers have not been fully elucidated. We have demonstrated that cholesterol expands when crystallizing and may trigger plaque rupture. Hypothesis: The present study evaluated the potential direct effects of Metoprolol Tartrate (MT) in altering cholesterol crystallization as a possible mechanism for plaque stabilization independent of its cardio-protective effect. Method: Cholesterol powder (3 g) was melted in 10-ml graduated cylinders with and without MT using a heat gun and then allowed to cool at room temperature. Doses of MT used were comparable to serum levels achieved in humans after a single dose of MT in graded doses of 100mg, 150mg and 200mg. This yielded a maximum serum concentration of 100ng/ml, 150ng/ml and 200ng/ml respectively. MT was dissolved in 1 ml of H2O and then diluted to the above concentrations and then added to cholesterol powder prior to melting. H2O alone was used as control. Five experiments were conducted at each concentration and...
The oncologist as genetic consultant: Two-year results in a large community-based practice
Authors: L. J. Geier, M. Sheehan, M. Elia, S. Ethirajan, E. Kent
Journal: Journal of Clinical Oncology (2009)

e22140 Background: Oncologists are in a unique position to provide effective genetic cancer risk assessment (GCRA). However, in most communities they defer this to genetic counselors (GC). At KC Cancer Center, a 35-MD community oncology group, the difficulty obtaining timely and effective GCRA became a quality of care issue. Methods: In December 2006 a new program was launched with 4 designated oncologists providing GCRA at 4 separate cancer centers. Each oncologist was responsible for gaining expertise in the common hereditary syndromes and appropriate interpretation of gene testing results prior to starting GCRA. Two-year results were analyzed. For those pts found to have deleterious mutations, charts were reviewed to confirm the gene affected, and the length of time between cancer dx and GCRA. Pts more than one year out from dx were designated as cancer survivors. Results: After 2 years, 490 pts had gone through gene testing after GCRA, and 85 were found to carry deleterious mutations. These data were compared to the previous three years when pts had been referred to GC ( Table ). Both the number of pts tested and the number with mutations in yrs 2007–8 were approximately 400% of the numbers for yrs 2005–06. Of the 85 pts with mutations, 51 (60%) were cancer survivors. Their median time from diagnosis was 5.5 yrs (range 1–25). 75/85 (88%) mutations were in a BRCA gene. Conclusions: This oncologist-centered model proved to be very effective in identifying mutation carriers, particularly among cancer survivors in whom the hereditary syndrome had been previously overlooked. Acceptance of this approach by pts, physicians, and payers has been extremely high. This model should be considered by oncology practices wanting to add GCRA to their service lines. [Table: see text] [Table: see text]
Abstract 17513: J Point Elevation and Cardiovascular Mortality: Insights From National Health And Nutrition Examination Survey-III
Authors: Vikas Singh, Nileshkumar J Patel, Apurva O Badheka, Ankit Rathod, Abhishek Deshmukh, George Marzouka, Tushar Tuliani, Mauro Moscucci, Mauricio Cohen
Journal: Circulation (2012)

Background:  The significance of early repolarization has recently been questioned with associated increased risk of cardiovascular mortality (CM). We assessed the prognostic significance of J point elevation (JPE) and its role in predicting CM in general population free of coronary artery disease or risk equivalents (CAD).   Methods:  Study population consisted of all adults >40 yo with EKG data available, enrolled into NHANES III (1988 to 1994). This self-weighting sample was representative of US population of 48138059 individuals with a follow-up period of 64497.75 person-years. Individuals with missing mortality data, history of coronary artery disease or equivalant, diabetes, peripheral artery disease, heart failure, stroke were excluded for this study. Patients with major ECG abnormalities, myocardial injury or infarction score>20, non-sinus rhythm, heart rate>120, QRS interval >120 and probable LVH were also excluded. All ECGs were computer- coded by the Minnesota coding. CM was linked to the National Death Index and was based on ICD-10. We divided the subjects into quartiles based on the sum of J point elevation in all leads.   Results:  Our dataset consisted of 4780 subjects with mean age of 57.28 ± 13.00 years (44.5% men and 88% whites). On multivariate analysis none of the quartiles were found to be significantly associated with CM after controlling for cardiovascular risk factors and serum electrolyte abnormalities (See Table). Subdivision of ECGs based on lead groups did not change this association Serum Calcium (p=0.05) and potassium (p   Conclusion:  We found no significant association between JPE and CM over long term follow-up in this cross-sectional United States population free from known heart disease. JPE may serve as a phenotype marker for underlying serum electrolyte abnormalities and not be the primary cause of CM.
Incidence of Brain Metastasis at the Initial Diagnosis of Lung Squamous Cell Carcinoma on the Basis of Stage, Excluding Brain Metastasis
Authors: Hyun Lee, Suk Hyeon Jeong, Byeong-Ho Jeong, Hye Yun Park, Kyung-Jong Lee, Sang-Won Um, O Jung Kwon, Hojoong Kim
Journal: Journal of Thoracic Oncology (2015)
Developing novel peptide inhibitors to chromosomal cohesion using mRNA display for nanodrug delivery in breast cancer therapy
Authors: Elizabeth O. McCullum, Debananda Pati
Journal: Clinical Cancer Research (2010)

Abstract Several specific molecular networks mediate the cellular proliferation of tumorigenic cells. One signaling pathway of interest is the transition from metaphase to anaphase which is dependent on cleavage of the cohesin protein complex by separase, an endopeptidase. A normal transition allows the protein complex to form, sister chromatid cleavage and the onset of anaphase. However, failure to properly assemble or maintain the integrity of this complex results in the premature separation of chromatids (PCS), mitotic arrest and apoptosis in cultured cells. This research effort will focus on the identification of cohesin Rad21, a proapoptotic protein that is over-expressed in breast cancer cells, mimcs for the induction of apoptosis in the cohesin-disrupted tumors. Using mRNA display, Rad21 mimetopes will be selected to bind a SMC-1 target in the formation of standard cohesin complex assembly. The pool of isolated peptides will be further characterized for their specificity, induction of PCS, mitotic arrest and apoptosis both in vitro and in vivo. Finally, peptides will be conjugated to a RAFT-peptide scaffold drug delivery system to exclusively target rapidly proliferating breast tumor cells. The potential advantages provide an area of promising therapeutics for antitumor effects when coupled with chemotherapy at the point of early detection.