bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topotecan: Weighing in When There Are Many Options
Authors: Penson Richard T. , Seiden Michael V. 
Published: October 2005

Abstract
The manuscript by Armstrong et al. in this issue of The Oncologist, reviewing the toxicity and efficacy of full-dose topotecan delivered as second-line therapy in individuals with small cell lung cancer or ovarian cancer, will likely serve as both the most comprehensive and the final review of this active agent delivered at the U.S. Food and Drug Administration–approved dosage and schedule. The review represents large, relative lyhomogeneous patient populations with prior platinum exposure and convincingly describes topotecan as an agent with activity that is comparable with those of all other approved drugs in this setting and a well-defined and relatively circumscribed set of toxicities. While the activity of topotecan in small cell carcinoma provides individuals with the hope for further palliation at the time of tumor recurrence, as discussed by Dr. Markman in this issue, the best use of this agent in the management of recurrent ovarian cancer is far from clear because, in part, of a growing list of approved active agents, most notably liposomal doxorubicin, gemcitabine, and weekly paclitaxel; a return to platinum; or a host of other agents such as vinorelbine, altretamine, irinotecan, docetaxel, etoposide, and others. The most pressing need is to accept that palliative therapies are designed to palliate and improve symptoms, and to move away from end points of radiologic and marker response to a focus on “clinical benefit” and clinically more meaningful end points.
Antibody-Based Therapies for Colorectal Cancer
Authors: Chung Ki Young , Saltz Leonard B. 
Published: October 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to: Select the appropriate clinical use of cetuximab and bevacizumab in the treatment of metastatic colorectal cancer based on the currently available clinical trial data and known toxicities of each agent.Discuss the controversy over EGFR testing in colorectal cancer patients and the lack of predictive value of EGFR expression by IHC.List the relevant clinical questions regarding the use of targeted agents in colorectal cancer that remain to be addressed by clinical trials.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
The recent successful development of novel monoclonal antibodies that target key components of biologic pathways has expanded the armamentarium of treatment options for patients with colorectal cancer. Two targets in particular–the process of new blood vessel development, or angiogenesis, and the epidermal growth factor receptor and its signaling pathway–are exploited by the newest monoclonal antibodies that are available for use in colorectal cancer patients. This clinical review focuses on the defining role of the two most clinically advanced novel agents, bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA, http://www.gene.com) and cetuximab (Erbitux®; ImClone Systems, Inc., New York, http://www.imclone.com), in colorectal cancer.
Combined Therapy with Weekly Irinotecan, Infusional 5-Fluorouracil and the Selective COX-2 Inhibitor Rofecoxib Is a Safe and Effective Second-Line Treatment in Metastatic Colorectal Cancer
Authors: Gasparini Giampietro , Gattuso Domenico , Morabito Alessandro , Longo Raffaele , Torino Francesco , Sarmiento Roberta , Vitale Stefano , Gamucci Teresa , Mariani Luigi 
Published: October 2005

AbstractThe purpose of this study was to determine the tolerability and activity of rofecoxib (Vioxx®; Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com) combined with weekly irinotecan (Camptosar®; Pfizer Pharmaceuticals, New York, http://www.pfizer.com) and infusional 5-fluorouracil (5-FU) as second-line therapy in metastatic colorectal cancer (MCRC). Enrolled patients had previously treated metastatic disease, were aged ≥18 to ≤75 years, and had adequate performance status. A cycle of treatment consisted of i.v. irinotecan on days 1, 8, 15, and 22, rofecoxib at an oral dose of 50 mg/day, and infusional 5-FU at a fixed dose of 200 mg/m2 per day for 5 weeks followed by 3 weeks of therapy with rofecoxib alone. In the dose-finding study, the starting dose of irinotecan was 87.5 mg/m2 and further dose escalations were planned by increments of 12.5 mg/m2 up to 125 mg/m2. Forty-eight consecutive patients were enrolled in the study. Among the 15 cases enrolled in the dose-finding study, one patient experienced grade 3 reversible diarrhea as the dose-limiting toxicity, at the fourth dose level tested. Therefore, the dose of irinotecan for the phase II study was 125 mg/m2, and 33 patients were enrolled and received a total of 75 cycles. Hematological side effects were moderate, with grade 4 neutropenia recorded in only two patients. The most common nonhematological toxicity was diarrhea, occurring in 25 patients (75.8%) and considered to be of grade 3 in 12 patients (36.4%). Sixteen patients achieved partial responses (48.5%; 95% confidence interval [CI], 30.8%–66.5%), and another 10 patients (30.3%) had stable disease. The median time to progression was 7 months (95% CI, 5–12) and the median overall survival (OS) was 18 months; the 1-year estimated OS rate was 69.4%. The unique schedule tested in this study is feasible, is well-tolerated, and has promising activity in patients with MCRC after progression on oxaliplatin (Eloxatin®; Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us)-based chemotherapy.
Thalidomide in Advanced Hepatocellular Carcinoma with Optional Low-Dose Interferon-α2a upon Progression
Authors: Schwartz Jonathan D. , Sung Max , Schwartz Myron , Lehrer Deborah , Mandeli John , Liebes Leonard , Goldenberg Alec , Volm Matthew 
Published: October 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to: Identify the etiologic factors contributing to the increasing incidence of hepatocellular carcinoma in the U.S.Explain the rationale for antiangiogenic therapeutic strategies in the treatment of hepatocellular carcinoma.Describe the clinical features associated with a particularly poor prognosis in unresectable hepatocellular carcinoma.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Purpose. To evaluate thalidomide in advanced hepatocellular carcinoma (HCC) and to evaluate combined thalidomide and low-dose interferon-α2a (IFN-α2a) after tumor progression on thalidomide. Systemic therapy is minimally effective in HCC and tumor angiogenesis is a potential therapeutic target.
Patients and Methods. Patients with unresectable HCC were eligible if they had preserved hepatic and renal function. The initial thalidomide dosage was 200 mg daily and was adjusted for toxicity. Upon progression, patients could continue thalidomide with additional low-dosage (one million units twice daily) IFN-α2a.
Results. Thirty-eight enrolled patients were predominantly hepatitis C virus infected (53%), Child-Pugh class A (79%), and Eastern Cooperative Oncology Group performance status 0–1 (92%); 60% had extrahepatic metastasis. Confirmed disease control was seen in seven patients (18%) and included one complete and one partial response (5% response rate). The median progression-free survival was 2.1 months, and median overall survival was 5.5 months. Tumor invasion of the portal vein or vena cava, large (&gt;10 cm) tumor, and younger age were associated with shorter overall survival. Toxicity included fatigue in 74% of patients. Six patients stopped therapy because of side effects, including two patients (5%) with grade 4 arteriothrombotic events. Five patients continued thalidomide upon progression with the addition of IFN-α2a; there was no disease control and 80% had grade 3 toxicity.
Conclusions. Thalidomide is not well tolerated and confers limited disease control in advanced HCC. Combination thalidomide and low-dose IFN-α2a is neither safe nor efficacious in this population.
Paclitaxel/Carboplatin/Etoposide Versus Paclitaxel/Topotecan for Extensive-Stage Small Cell Lung Cancer: A Minnie Pearl Cancer Research Network Randomized, Prospective Phase II Trial
Authors: Greco F. Anthony , Thompson Dana S. , Morrissey Lisa H. , Erland Joan B. , Burris Howard A. , Spigel David R. , Joseph Geetha , Corso Steven W. , Spremulli Ellen , Hainsworth John D. 
Published: October 2005

Abstract
Purpose. To compare the combination of paclitaxel (Taxol®; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and topotecan (Hycamtin®; Glaxo SmithKline, Philadelphia, http://www.gsk.com) with paclitaxel, carboplatin (Paraplatin®; Bristol-Myers Squibb), and etoposide (Etopophos®, VePesid®; Bristol-Myers Squibb) in patients with previously untreated extensive-stage small cell lung cancer.
Patients and Methods. In this phase II trial, 120 patients were randomly allocated to receive either topotecan (1.5 mg/m2 i.v. days 1, 2, and 3) and paclitaxel (175 mg/m2 i.v. day 1) every 21 days orpaclitaxe l (200mg/m2 i.v. day 1), carboplatin (area under the concentration–time curve 6 i.v. day 1), and etoposide (50 mg/100 mg alternating daily by mouth days 1–10) every 21 days, each regimen for a maximum of eight cycles. The primary end points were objective response rate and time to progression.
Results. The paclitaxel–carboplatin–etoposide combination produced a significantly higher overall response rate (78% versus 48%), longer median time to progression (7.6 months versus 5.5 months), and greater number of patients free from progression at 1 year (14% versus 8%) compared with paclitaxel plus topotecan. There was no difference in overall survival. Toxicities were similar in the two treatment arms.
Conclusions. The paclitaxel–carboplatin–etoposide combination produced a superior overall response rate and time to progression in patients with extensive-stage small cell lung cancer compared with paclitaxel plus topotecan. The platinum compounds continue to be a necessary component of the initial therapy for these patients.
Multifocal Extranodal Non-Hodgkin Lymphoma: A Clinicopathologic Study of 37 Cases in Greece, a Hellenic Cooperative Oncology Group Study
Authors: Economopoulos Theofanis , Papageorgiou Sotirios , Rontogianni Dimitra , Kaloutsi Vassiliki , Fountzilas George , Tsatalas Constantinos , Pavlidis Nikolaos , Pectasides Dimitrios , Papageorgiou Efstathios , Dimopoulos Meletios 
Published: October 2005

Abstract
The purpose of this retrospective study was to illustrate the clinicopathological features of patients presenting with multifocal extranodal non-Hodgkin lymphoma (NHL). Among 810 patients with NHL, 37 cases (4.2%) were found to have multiple extranodal involvement (two or more sites). There were 24 men and 13 women, with a median age of 63 years. The majority of these cases (n = 26) had gastric or intestinal (GI) involvement with or without other extranodal sites. Lung along with another extranodal site was relatively common in the present series. Stratification of the 37 cases according to the International Prognostic Index (IPI) showed that 89% of the patients belonged to the high-risk groups. Diffuse large-B-cell lymphoma (DLBCL) accounted for 62%, and mucosa-associated lymphoma tissue (MALT) lymphoma accounted for 27% of all cases. After induction treatment with anthracycline-based regimens, complete remission was achieved in 21 patients (57%), partial remission was achieved in six patients (16%), and seven patients (19%) had no response, while three patients (8%) were nonevaluable. In conclusion, multifocal extranodal NHL is a heterogeneous group of diseases. The majority of them arise at various sites in the GI tract. DLBCL was the most frequent histological subtype followed by MALT lymphoma. Risk group, as defined by the IPI, was predictive of survival.
Helping Melanoma Patients Decide Whether to Choose Adjuvant High-Dose Interferon-α2b
Authors: Hurley Karen E. , Chapman Paul B. 
Published: October 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the benefits of adjuvant high-dose interferon-α therapy to melanoma patients.List the toxicities most commonly associated with adjuvant high-dose interferon-α therapy in melanoma patients.Assist patients with melanoma to decide whether to choose adjuvant high-dose interferon-α therapy.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
High-dose interferon-α2b is a U.S. Food and Drug Administration–approved adjuvant treatment for stage III melanoma, and yet, because of its limited efficacy and well-known toxicity, it is not universally accepted by patients and oncologists. In this paper, we evaluate the benefits and risks of adjuvant high-dose interferon-α2b and try to provide a framework to help oncologists guide patients trying to decide whether to undergo adjuvant high-dose interferon therapy.
The Molecular Perspective: c-Abl Tyrosine Kinase
Authors: Goodsell David S. 
Published: October 2005

Learning Objectives
After completing this course, the reader will be able to: Discuss c-Abl and Bcr-Abl and their role in cancer chemotherapy.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Enhanced Hole Mobility in Regioregular Polythiophene Infiltrated in Straight Nanopores
Authors: Coakley K. M. , Srinivasan B. S. , Ziebarth J. M. , Goh C. , Liu Y. , McGehee M. D. 
Published: October 2005

AbstractWe demonstrate that the hole mobility in regioregular poly(3‐hexylthiophene) can be enhanced by a factor of 20 by infiltrating it into straight nanopores of anodic alumina. Optical characterization shows that the polymer chains are partially aligned in the charge‐transport direction.
SPME Sampling of BTEX before GC/MS Analysis: Examples of outdoor and indoor Air Quality Measurements in Public and Private Sites
Authors: Tumbiolo Simonetta , Gal Jean‐François , Maria Pierre‐Charles , Zerbinati Orfeo 
Published: October 2005

AbstractThis article presents the results of an exploratory application of the Solid Phase MicroExtraction (SPME) technique to the analysis of BTEX (benzene, toluene, ethylbenzene and xylenes) at the μg/m3 level in outdoor and indoor air. The salient features of the method validation are reported. As shown by the various examples of field sampling described, SPME technique appears as a method of choice for fast qualitative analysis and quantitative determination of Volatile Organic Compounds (VOC). The small dimensions of the SPME sampling system and the short sampling time let envisage its utilisation for the rapid diagnostic of outdoor and indoor air quality.
Evaluation of Mutual Connections between Zero‐Valent Iron Reactivity and Groundwater Composition in Trichloroethylene Degradation
Authors: Zanetti Maria Chiara , Fiore Silvia 
Published: October 2005

AbstractZero‐valent iron Permeable Reactive Barriers (PRBs) are an efficient and relatively low cost in situ technology for the remediation of aquifers polluted by chlorinated solvents. The groundwater composition and the zero‐valent iron reactive material are linked by mutual connections. The groundwater, to a certain extent depending on its composition, is able to oxidize the metallic iron, thus decreasing its reactivity; on the other hand, the dechlorination process and the leaching of chemical species from the reactive substrate may deeply modify groundwater composition. In this study the results of some batch and leaching column tests, performed by means of Connelly iron (Environmental Technologies Inc., Canada) and different aqueous phases (distilled water and an artificial groundwater) are compared, to evaluate the influence of groundwater composition on the reactivity of the iron material for trichloroethylene (TCE) remediation. The degradation mechanisms of the pollutant are discussed. On the grounds of the gathered results the aqueous phase composition shows a strong influence on TCE degradation kinetics obtained by means of Connelly iron; in fact the presence of dissolved substances accelerates TCE degradation.
Determination of Aflatoxins in Peanuts, Maize Feed and Whole Milk by HPLC‐MS2 and MS3 Tandem Mass Spectrometry
Authors: Pazzi Marco , Medana Claudio , Brussino Mariacarla , Baiocchi Claudio 
Published: October 2005

AbstractA method is presented for the detection of six toxins of fungal origin in various foods: peanuts, a sample of maize feed and whole milk. Extraction and HPLC‐APCI‐MS detection were discussed. The performances of MS/MS, MS3 and SRM detection modes were checked and best conditions of sensitivity were obtained in MS/MS mode.
Analysis of Voltammetric Data for the Evaluation of Seasonal Changes of the Ni, Cd, Pb and Cu Content in Atmospheric Particulate PM2.5
Authors: Giannetto Marco , Alfieri Enrica , Giugliano Michele , Lonati Giovanni , Mori Giovanni , Pizzol Massimo 
Published: October 2005

AbstractIn this paper, the preliminary results of a study on concentration of heavy metals in PM2.5 (atmospheric particles with aerodynamic diameter less than 2.5 μm) fractions of atmospheric particulate matter, sampled in Milan, are presented. This work aims to develop an electroanalytical method to analyse Pb, Cu, Cd and Ni in PM2.5 and to investigate seasonal and weekly trends in the amount of PM2.5 and its composition for considered metals. The samples have been selected within the seasons ranging from September 2002 to November 2003 so that they represent the possible seasonal changes; the samples within this period have been chosen in order to have data relevant to both working days and holidays. The determination of Cd, Pb and Cu has been carried out by Differential Pulse Anodic Stripping Voltammetry, whereas the concentration of Ni has been determined by Differential Pulse Adsorptive Cathodic Stripping Voltammetry. The concentrations of the metals in the sampled atmosphere and in the PM2.5 have been evaluated; through ANOVA possible seasonal or weekly variations in the above cited concentrations have been investigated.
Turner syndrome: Four challenges across the lifespan
Authors: Sutton Erica J. , McInerney‐Leo Aideen , Bondy Carolyn A. , Gollust Sarah E. , King Donnice , Biesecker Barbara 
Published: October 2005

AbstractTurner syndrome (TS) is a sex chromosome condition that occurs in approximately 1/2,500 live female births. Despite the prevalence of this chromosomal condition, the challenges these women face throughout their lives are not fully understood. This qualitative research study aimed to characterize the subjective experiences of individuals with TS throughout their lifespan, to investigate their concerns and obstacles, and to offer insight into the strengths and weaknesses of health care delivery, as they perceived them. Ninety‐seven girls and women with TS and 21 parents consented to participate in this interview study. Interviews were semi‐structured and open‐ended in design. Questions sought to elicit responses relating to existing concerns associated with their condition and positive and negative health care experiences. Participants were divided into four age categories (childhood, adolescence, adulthood, and mature adulthood) to facilitate a comparative analysis across the age spectrum. Regardless of age, infertility was the most frequently cited concern followed closely by short stature. Sexual development and function and general health were also viewed as challenges by a number of participants in each age group. Although the relative weight of these four concerns tended to shift based upon the individual's age and life experiences, all four issues remained significant throughout the lifespan. Enhanced awareness of the evolving physical and psychological challenges faced by girls and women with TS may help health care providers (HCPs) improve the quality of life for these individuals. Published 2005 Wiley‐Liss, Inc.
Aberrant seizure‐induced neurogenesis in experimental temporal lobe epilepsy
Authors: Parent Jack M. , Elliott Robert C. , Pleasure Samuel J. , Barbaro Nicholas M. , Lowenstein Daniel H. 
Published: October 2005

AbstractNeurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure‐induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox‐1 immunohistochemistry and pulse‐chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure‐induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. Ann Neurol 2005
Design, Synthesis and Analysis of Inhibitors of Bacterial Aspartate Semialdehyde Dehydrogenase
Authors: Cox Russell J. , Gibson Jennifer S. , Hadfield Andrea T. 
Published: October 2005

AbstractUnsaturated and fluorinated analogues of aspartyl‐β‐phosphate were synthesised as potential inhibitors of the bacterial enzyme aspartate semialdehyde dehydrogenase (ASA‐DH). Acetylenic and Z‐olefinic analogues showed competitive inhibition, but an E‐olefinic analogue was inactive. A monofluoromethylene phosphonate competed poorly, but showed time‐dependent inhibition of ASA‐DH in the absence of phosphate. Simulated docking procedures were used to rationalise the results. These studies showed that substrate and inhibitor binding are mediated by interaction with two active‐site arginine residues, and for likely covalent attachment to the active‐site thiol group, electrophilic carbon atoms should be located 4.5 Å, or less, from the thiol.