bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐performance liquid chromatography with ﬂuorescence detection for the simultaneous determination of 3,4‐methylenedioxymethamphetamine, methamphetamine and their metabolites in human hair using DIB‐Cl as a label
Authors: Kaddoumi Amal , Kikura‐Hanajiri Ruri , Nakashima Kenichiro
Published: March 2004

This paper describes a highly sensitive HPLC method for the simultaneous determination of 3,4‐methylenedioxymethamphetamine (MDMA), 3,4‐methylenedioxyamphetamine (MDA), amphetamine (AP) and methamphetamine (MP) in human hair samples. The amphetamines investigated were derivatized with the ﬂuorescent reagent, DIB‐Cl to yield highly ﬂuorescent DIB‐derivatives, which were then analyzed by HPLC with ﬂuorescence detection at excitation and emission wavelengths of 325 nm and 430 nm, respectively. The separation was achieved on an ODS column with an isocratic mobile phase composed of acetonitrile‐methanol‐water (30:40:30, v/v/v). The limits of detection for the four compounds obtained by the proposed method ranged from 11 to 200 pg/mg. The method was successfully applied to the determination of MDMA and MDA in hair samples obtained from MDMA abuser. Copyright © 2004 John Wiley & Sons, Ltd.
Syntheses and Reactions of Hexavalent Organotellurium Compounds Bearing Five or Six TelluriumCarbon Bonds
Authors: Miyasato Masataka , Sagami Takao , Minoura Mao , Yamamoto Yohsuke , Akiba Kin‐ya
Published: March 2004

A variety of hexaorganotellurium compounds, Ar6−n(CH3)nTe [Ar=4‐CF3C6H4, n=0 (1 a), n=1 (3 a), n=2 (trans‐4 a and cis‐4 a), n=3 (mer‐5 a), n=4 (trans‐6 a); Ph, n=0 (1 b), n=1 (3 b), n=2 (trans‐4 b); 4‐CH3C6H4, n=0 (1 c), n=1 (3 c), n=2 (trans‐4 c), n=4 (trans‐6 c); 4‐BrC6H4, n=0 (1 d)] and Ar5(R)Te [Ar=4‐CF3C6H4, R=4‐CH3OC6H4 (8); Ar=4‐CF3C6H4, R=vinyl (9), Ar=Ph, R=vinyl (10), Ar=4‐CF3C6H4, R=PhSCH2 (11), Ar=Ph, R=PhSCH2 (12), Ar=4‐CF3C6H4, R=nBu (13)] and pentaorganotellurium halides, Ar5TeX [Ar=4‐CF3C6H4, X=Cl (2 a‐Cl), X=Br (2 a‐Br); Ar=Ph, X=Cl (2 b‐Cl), X=Br (2 b‐Br); Ar=4‐CH3C6H4, X=Cl (2 c‐Cl), X=Br (2 c‐Br); Ar=4‐BrC6H4, X=Br (2 d‐Br)] and (4‐CF3C6H4)4(CH3)TeX [X=Cl (trans‐7 a‐Cl) and X=Br (trans‐7 a‐Br)] were synthesized by the following methods: 1) one‐pot synthesis of 1 a, 2) the reaction of SO2Cl2 or Br2 with Ar5Te−Li+ generated from TeCl4 or TeBr4 with five equivalents of ArLi, 3) reductive cleavage of Ar6−m(CH3)mTe (m=0 or 2) with KC8 followed by treatment with CH3I, 4) valence expansion reaction from low‐valent tellurium compounds by treatment with KC8 followed by reaction with CH3I, 5) nucleophilic substitution of Ar6−y−z(CH3)zTeXy−z (X=Cl, Br, OTf; z=0, 1; y=1, 2) with organolithium reagents. The scope and limitations and some details for each method are discussed and electrophilic halogenation of the hexaorganotellurium compounds is also described.
Synthesis of C3 Benzo[1,2‐e:3,4‐e′:5,6‐e′′]tribenzo[l]acephenanthrylenes (“Crushed Fullerene” Derivatives) by Intramolecular Palladium‐Catalyzed Arylation
Authors: Gómez‐Lor Berta , González‐Cantalapiedra Esther , Ruiz Marta , de Frutos Óscar , Cárdenas Diego J. , Santos Amelia , Echavarren Antonio M.
Published: March 2004

The C60 polyarenes 4, 5, 18 a, and 18 b have been synthesized from truxene by triple alkylation at C5, C10, and C15 followed by a palladium‐catalyzed intramolecular arylation. The synthesis of “crushed fullerene” C60H30 (2) is the most efficient reported to date and proceeds in 33 % overall yield.
[K36(μ6‐Cl)2 (H2O)11(MeOH)32][SnSe4] [Co4(μ4‐Se)(SnSe4)4] 3: Synthesis and Crystal Structure of a Novel Compound Containing Ternary [Co4(μ4‐Se)(SnSe4)4] 10‐ Anions and a Novel [(μ6‐Cl)2K9]7+ Coordination Aggregate.
Authors: Melullis Maike , Zimmermann Christian , Anson Christopher E. , Dehnen Stefanie
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
A Facile Diastereoselective Synthesis of Functionalized 1,2,3‐Trisubstituted Benzocyclopentenes Through the Cycloaddition of Bis(phenylsulfonyl)iodonium Ylides to Cyclic Alkenes.
Authors: Adam Waldemar , Gogonas Efstathios P. , Hadjiarapoglou Lazaros P.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Tethered [2 + 2 + 2] Cycloaddition Reactions of Cobalt—Cycloheptyne Complexes.
Authors: Mohamed Ahmed B. , Green James R.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Styrylbenzofuran Derivatives as Styrylquinoline Analogues for HIV‐1 Integrase Inhibitor.
Authors: Yoo Ho , Lee Jae Yeol , Park Jang Hyun , Chung Bong Young , Lee Yong Sup
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Polyfluorophenyl Substituted‐4,5‐dihydropyrazole Derivatives via 1,3‐Dipolar Cycloaddition of Nitrile Imine with Ethyl Acrylate.
Authors: Song Li‐Ping , Zhu Shi‐Zheng
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
A New Synthesis of Flavonoids via Heck Reaction.
Authors: Bianco Armandodoriano , Cavarischia Claudia , Farina Angela , Guiso Marcella , Marra Carolina
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of α‐Trifluoromethylated Nitrogen Heterocycles.
Authors: Gille Segolene , Ferry Aurelien , Billard Thierry , Langlois Bernard R.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Substituted Azoloquinolines and ‐quinazolines as New Potent Farnesyl Protein Transferase Inhibitors.
Authors: Angibaud Patrick , et al. et al.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Bridged Azabicyclic Structures via Ring‐Closing Olefin Metathesis.
Authors: Neipp Christopher E. , Martin Stephen F.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
The First Nonthiolic, Odorless 1,3‐Propanedithiol Equivalent and Its Application in Thioacetalization.
Authors: Liu Qun , Che Guangbo , Yu Haifeng , Liu Yingchun , Zhang Jingping , Zhang Qian , Dong Dewen
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of 1,4,6‐Trisubstituted 2[1H]‐Pyrimidineselenones.
Authors: Zylewska Alicja , Tejchman Waldemar , Korohoda Maria J. , Zylewski Marek
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis, Structural Characterization and in vitro Antitumor Activity of 4‐Dimethylaminopyridinium (6‐Chloro‐1,1‐dioxo‐1,4,2‐benzodithiazin‐3‐yl)methanides.
Authors: Brzozowski Zdzislaw , Saczewski Franciszek , Gdaniec Maria
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Reaction of 5‐Halo‐1,2,3‐thiadiazoles with Aliphatic Diamines. Synthesis and Intramolecular Cyclization of Bis(1,2,3‐triazolyl‐1,2,3‐thiadiazolyl)sulfides.
Authors: Volkova Natalya N. , Tarasov Evgeniy V. , Kodess Mikhail I. , Van Meervelt Luc , Dehaen Wim , Bakulev Vasiliy A.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Silenes as Novel Synthetic Reagents: Synthesis of Diols and Lactones from Simple Alkyldienes.
Authors: Berry Malcolm B. , Griffiths Russel J. , Sanganee Mahesh J. , Steel Parick G. , Whelligan Daniel K.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Rhodium‐Catalyzed Regio‐ and Stereoselective 1‐Seleno‐2‐thiolation of Alkynes.
Authors: Arisawa Mieko , Kozuki Yoshihiro , Yamaguchi Masahiko
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Steroids from the Underground Parts of Trillium kamtschaticum.
Authors: Ono Masateru , Yanai Yoshihiro , Ikeda Tsuyoshi , Okawa Masafumi , Nohara Toshihiro
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Macrocyclic Derivatives Containing a Sucrose Unit.
Authors: Jarosz Slawomir , Listkowski Arkadiusz
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Furoquinoline Alkaloids from Teclea nobilis.
Authors: Al‐Rehaily Adnan J. , Ahmad Mohammad S. , Muhammad Ilias , Al‐Thukair Assad A. , Perzanowski Herman P.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthetic Studies on Ecteinascidin 743: Rapid Access to the Fully Functionalized Tetrahydroisoquinoline with a Bridged 10‐Membered Sulfur Containing Macrocycle.
Authors: De Paolis Michael , Chiaroni Angele , Zhu Jieping
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis of Hydroxymethyl Branched [3.2.0]Bicyclic Nucleosides Using a Regioselective Oxetane Ring‐Formation.
Authors: Christensen Nanna K. , Andersen Ann Katrine L. , Schultz Trine R. , Nielsen Poul
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and anti‐HBV Activity of Thiouracils Linked via S and N‐1 to the 5‐Position of Methyl β‐D‐Ribofuranoside.
Authors: Abdel‐Rahman Adel A.‐H. , Abdel‐Megied Ahmed E.‐S. , Goda Adel E.‐S. , Zeid Ibrahim F. , El Ashry El Sayed H.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Antibiotics from Gliding Bacteria. Part 94. Cyrmenins, New β‐Methoxyacrylate Inhibitors of the Electron Transport. Production, Isolation, Physico‐Chemical and Biological Properties.
Authors: Sasse Florenz , Leibold Thomas , Kunze Brigitte , Hoefle Gerhard , Reichenbach Hans
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and Biological Activity of AM‐112 and Related Oxapenem Analogues.
Authors: Simpson Iain N. , Urch Christopher J. , Hagen Gudrun , Albrecht Ralf , Sprinkart Birgit , Pfaendler Hans R.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Lanopylins A1, B1, A2 and B2, Novel Lanosterol Synthase Inhibitors from Streptomyces sp. K99‐5041.
Authors: Sakano Yuichi , Shibuya Masaaki , Matsumoto Atsuko , Takahashi Yoko , Tomoda Hiroshi , Omura Satoshi , Ebizuka Yutaka
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
SMTP‐4D, ‐5D, ‐6D, ‐7D and ‐8D, a New Series of the Non‐Lysine‐Analogue Plasminogen Modulators with a D‐Amino Acid Moiety.
Authors: Hu Weimin , Kitano Yoshikazu , Hasumi Keiji
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Carbon Nanotube/CdS Core—Shell Nanowires Prepared by a Simple Room‐Temperature Chemical Reduction Method.
Authors: Cao Jian , Sun Jing‐Zhi , Hong Jian , Li Han‐Ying , Chen Hong‐Zheng , Wang Mang
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Polyoxolenes May Provide a Tool for Designing Paramagnetic Molecules with Predetermined Spin Topologies
Authors: Bencini Alessandro , Caneschi Andrea , Dei Andrea , Gatteschi Dante , Sangregorio Claudio , Shultz David , Sorace Lorenzo , Vaz Maria G. F.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Palladium‐Catalyzed Cross‐Coupling Reactions and Electrocyclizations—Efficient Combinations for New Cascade Reactions.
Authors: de Meijere Armin , Schelper Michael , Knoke Mario , Yucel Baris , Suennemann Hans Wolf , Scheurich Rene Peter , Arve Lars
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Reactivity Control in Palladium‐Catalyzed Reactions: A Personal Account.
Authors: Kocovsky Pavel
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Modification of Macrocyclic Compounds by Azaheterocycles
Authors: Itsikson Nadezhda A. , Rusinov Gennady L. , Beresnev Dmitry G. , Chupakhin Oleg N.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Recent Studies on 1,3‐Dipolar Cycloadditions of Nitrones
Authors: Banerji Avijit , Sengupta Piyali
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Microwave‐Enhanced Radiochemistry
Authors: Jones John R. , Lu Shui‐Yu
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Comments on Recent Achievements in Biomimetic Organic Synthesis.
Authors: de la Torre Maria C. , Sierra Miguel A.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Recent Developments and Advances in Formulations and Applications of Chemical Reagents Used in Froth Flotation
Authors: Urbina R. Herrera
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Comparison Between Reactions Induced by UV/VIS Photons and Ionizing Radiation in Hydrocarbon‐Like Media
Authors: Brown Gerald O. , Weiss Richard G.
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
New Mass Spectrometric Methods for the Quantification of Protein—Ligand Binding in Solution.
Authors: Breuker Kathrin
Published: April 2004

For Abstract see ChemInform Abstract in Full Text.
Recall and detection rates in screening mammography
Authors: Gur David , Sumkin Jules H. , Hardesty Lara A. , Clearfield Ronald J. , Cohen Cathy S. , Ganott Marie A. , Hakim Christiane M. , Harris Kathleen M. , Poller William R. , Shah Ratan , Wallace Luisa P. , Rockette Howard E.
Published: March 2004

BACKGROUND

The authors investigated the correlation between recall and detection rates in a group of 10 radiologists who had read a high volume of screening mammograms in an academic institution.

METHODS

Practice‐related and outcome‐related databases of verified cases were used to compute recall rates and tumor detection rates for a group of 10 Mammography Quality Standard Act (MQSA)‐certified radiologists who interpreted a total of 98,668 screening mammograms during the years 2000, 2001, and 2002. The relation between recall and detection rates for these individuals was investigated using parametric Pearson (r) and nonparametric Spearman (rho) correlation coefficients. The effect of the volume of mammograms interpreted by individual radiologists was assessed using partial correlations controlling for total reading volumes.

RESULTS

A wide variability of recall rates (range, 7.7–17.2%) and detection rates (range, 2.6–5.4 per 1000 mammograms) was observed in the current study. A statistically significant correlation (P < 0.05) between recall and detection rates was observed in this group of 10 experienced radiologists. The results remained significant (P < 0.05) after accounting for the volume of mammograms interpreted by each radiologist.

CONCLUSIONS

Optimal performance in screening mammography should be evaluated quantitatively. The general pressure to reduce recall rates through “practice guidelines” to below a fixed level for all radiologists should be assessed carefully. Cancer 2004. © 2004 American Cancer Society.
Predictors of prostate‐specific antigen progression among men with seminal vesicle invasion at the time of radical prostatectomy
Authors: Freedland Stephen J. , Aronson William J. , Presti Joseph C. , Amling Christopher L. , Terris Martha K. , Trock Bruce , Kane Christopher J.
Published: March 2004

BACKGROUND

Seminal vesicle (SV) invasion at the time of radical prostatectomy (RP) generally is considered to be indicative of poor outcome. The authors examined whether there was a subset of men with SV invasion who had long‐term prostate‐specific antigen (PSA) progression–free survival.

METHODS

Data were examined from 1687 men who underwent RP between 1988 and 2002 at 5 equal‐access medical centers. Patients were grouped based on the presence or absence of SV invasion at the time of RP. Clinical and pathologic variables as well as biochemical outcome data were compared across the groups using rank‐sum, chi‐square, and log‐rank tests. Multivariate Cox proportional hazards analysis was used to determine the significant predictors of time to PSA failure among men with SV invasion.

RESULTS

Men with SV invasion had significantly higher PSA values, higher clinical stage, higher grade tumors, and were more likely to have concomitant extracapsular extension or a positive surgical margin. The 5‐year PSA progression–free rates for men who had SV invasion was 36%, compared with 70% among men who had no SV invasion. Among men who had SV invasion, using multivariate analysis, only age (P = 0.023), pathologic Gleason score (P = 0.041), and surgical margin status (P = 0.019) were found to be independent predictors of PSA failure. By combining significant prognostic variables, the authors identified a subset of men with SV invasion, low‐grade tumors (Gleason score 2–6), and negative surgical margins who had a 5‐year PSA progression–free rate of 69%. Men with SV invasion, Gleason scores 2–6 tumors, negative surgical margins, and age ≥ 60 years (n = 11; 8%) had a 5‐year PSA progression–free rate of 100%.

CONCLUSIONS

Although the majority of men with SV invasion have high‐grade disease and a short time to biochemical failure, the authors identified a subset of men with low‐grade disease, negative surgical margins, and older age who, despite SV invasion, had an extremely favorable clinical course. Thus, SV invasion does not uniformly suggest an unfavorable prognosis. prognosis. Cancer 2004. © 2004 American Cancer Society.
Biochemical failure after radical prostatectomy in men with pathologic organ‐confined disease: pT2a versus pT2b
Authors: Freedland Stephen J. , Partin Alan W. , Epstein Jonathan I. , Walsh Patrick C.
Published: March 2004

BACKGROUND

The 1997 TNM staging system for prostate carcinoma defines a pT2a disease as a tumor histologically involving one lobe of the prostate and pT2b disease as a tumor histologically involving both prostatic lobes. Whether this distinction provides prognostic significance is unclear. The authors evaluated biochemical outcomes between men with pT2aN0 and pT2bN0 disease.

METHODS

The authors identified 1606 men with organ‐confined disease (pT2N0) who were treated with radical prostatectomy between 1982 and 2003 by one surgeon. Clinical characteristics were compared between men with pT2a and pT2b tumors using rank‐sum analysis, and prostate‐specific antigen (PSA) recurrence data were compared using log‐rank analysis. The significant independent predictors of PSA recurrence were determined using a multivariate Cox proportional hazards model.

RESULTS

There were no significant differences between men with pT2a and pT2b tumors at the time of surgery in terms of clinicopathologic characteristics (biopsy and pathologic Gleason score, serum PSA level, clinical stage, and age). Log‐rank analysis revealed no significant differences in time to PSA recurrence between men with pT2a and pT2b tumors (P = 0.755). The 10‐year PSA progression‐free survival rate was 95% (confidence interval [CI], 92–97%) for men with pT2a tumors and 93% (CI, 90–95%) for men with pT2b tumors. Multivariate analysis showed that the significant predictors of PSA recurrence included serum PSA level, biopsy and pathologic Gleason score, and clinical stage. In the current cohort of men with organ‐confined disease, pathologic stage (pT2a vs. pT2b) was not a significant predictor of PSA recurrence on multivariate analysis.

CONCLUSIONS

There was no difference in PSA recurrence rates between men with pT2aN0 versus pT2bN0 tumors. In men with organ‐confined disease, radical prostatectomy provided excellent 10‐year PSA progression‐free survival regardless of tumor burden (pT2a vs. pT2b). Consideration should be given to modifying the TNM staging system to eliminate substratification of pT2 tumors. Cancer 2004. © 2004 American Cancer Society.
Dysplasia in Barrett esophagus
Authors: Lao Christopher D. , Simmons Melanie , Syngal Sapna , Bresalier Robert S. , Fortlage Laurie , Normolle Daniel , Griffith Kent A. , Appelman Henry D. , Brenner Dean E.
Published: March 2004

BACKGROUND

Dysplasia in Barrett esophagus is a premalignant condition that is associated with an increased risk of developing esophageal adenocarcinoma. Unfortunately, clinical investigation aimed at prevention of progression to malignant disease has been hampered by the variable prevalence of dysplasia reported in the literature. The objective of the current study was to more accurately determine the prevalence of dysplasia among individuals with Barrett esophagus who would be available for enrollment in a chemoprevention trial.

METHODS

The pathology archives of 3 institutions were reviewed over a 5‐year period for all reports of diagnoses of Barrett esophagus. Surgical cases, malignancies, and duplicate or referral cases were excluded from the analysis.

RESULTS

A total of 790 cases of Barrett esophagus were identified. Of these, 37 (4.7%) were cases of low‐grade dysplasia (LGD), and 20 (2.5%) were cases of high‐grade dysplasia. The University of Michigan Medical Center (Ann Arbor, MI) diagnosed 18 cases of LGD, Henry Ford Hospital (Detroit, MI) diagnosed 15 cases of LGD, and Brigham and Women's Hospital (Boston, MA) diagnosed 4 cases of LGD in patients with Barrett esophagus over the 5‐year study period.

CONCLUSIONS

The confirmed low prevalence of cases of LGD will affect the design of future clinical trials of chemopreventive interventions for Barrett esophagus. Cancer 2004. © 2004 American Cancer Society.
ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas
Authors: Streiff Michael B. , Segal Jodi , Grossman Stuart A. , Kickler Thomas S. , Weir Edward G.
Published: March 2004

BACKGROUND

Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with malignant gliomas. To investigate the pathogenesis of VTE and facilitate targeted prophylaxis strategies, the authors aimed to characterize VTE risk factors in these patients.

METHODS

The authors conducted a retrospective chart review of 130 adult patients with glioma who received their primary therapy at the Johns Hopkins Hospital (Baltimore, MD) between 1991 and 2001. Symptomatic VTE was confirmed by objective radiologic testing. The association between clinical and laboratory characteristics and VTE was assessed using parametric and nonparametric statistical tests and survival analysis.

RESULTS

VTE developed in 28 patients (21.5%) at a median of 4.8 months after diagnosis (interquartile range, 2.1–13.2). Patients with tumors > 5 cm were more likely to develop VTE than patients with smaller tumors (hazard ratio = 2.2; P = 0.04). For every year increase in age, the hazard ratios for thrombosis increased by 3% (P = 0.011). When stratified by ABO blood group, the hazard ratios for thrombosis were 2.7 and 9.4 for patients with blood groups A (P = 0.045) and AB (P < 0.0001), respectively, compared with patients with blood group O. No association was observed between VTE and the other patient characteristics analyzed.

CONCLUSIONS

Patient age, tumor size, and particularly ABO blood group are risk factors for VTE among patients with malignant gliomas. These findings may facilitate the development of a thrombosis risk score that will allow physicians to individualize VTE prophylaxis regimens. Cancer 2004. © 2004 American Cancer Society.
New systemic frontline treatment for metastatic colorectal carcinoma
Authors: Braun Ada H. , Achterrath Wolf , Wilke Hansjochen , Vanhoefer Udo , Harstrick Andreas , Preusser Peter
Published: March 2004

Options for first‐line chemotherapy in patients with metastatic colorectal carcinoma have broadened considerably with the introduction of irinotecan and oxaliplatin. Furthermore, the oral fluoropyrimidine capecitabine has demonstrated efficacy in Phase III trials and recently was approved for first‐line treatment in Europe and the United States. Capecitabine yielded similar median times to disease progression and median survival rates compared with bolus 5‐fluorouracil (5‐FU)/leucovorin (LV) (Mayo Clinic/North Central Cancer Treatment Group regimen), with superior and similar response rates, respectively. However, its role as a first‐line, single‐agent substitute for intermittent infusional 5‐FU/LV remains to be defined. The addition of irinotecan or oxaliplatin to 5‐FU/LV resulted in improved response rates and progression‐free survival in large, randomized trials; moreover, irinotecan‐containing regimens resulted in improved overall survival. Prevalent regimens of irinotecan/5‐FU/LV and oxaliplatin/5‐FU/LV have been compared in two randomized Phase III trials. One study demonstrated the statistical superiority of oxaliplatin/infusional 5‐FU/LV over irinotecan/bolus 5‐FU/LV in terms of response, time to disease progression, and median survival; however, those advantages may have been attributable to infusional administration or to major differences in second‐line therapy. A randomized Phase III study comparing irinotecan and oxaliplatin in combination with the same infusional 5‐FU/LV regimens and crossover in case of disease progression showed equivalent efficacy for both schedules in the first‐line setting, but the irinotecan combination proved beneficial in terms of safety. New molecular targeted agents, such as angiogenesis‐modulating compounds (e.g., bevacizumab) and epidermal growth factor receptor inhibitors (e.g., cetuximab), are under clinical investigation. This review updates current systemic frontline treatments and future perspectives for patients with advanced colorectal carcinoma. Cancer 2004. © 2004 American Cancer Society.
Laparoscopic fluorescence detection of ovarian carcinoma metastases using 5‐aminolevulinic acid‐induced protoporphyrin IX
Authors: Löning Martin , Diddens Heyke , Küpker Wolfgang , Diedrich Klaus , Hüttmann Gereon
Published: March 2004

BACKGROUND

The aim of the current clinical study was to evaluate the in vivo fluorescence detection of ovarian carcinoma metastases in a second‐look laparoscopic procedure after intraperitoneally applied 5‐aminolevulinic acid (ALA).

METHODS

Five hours before laparoscopic surgery, ALA was applied intraperitoneally via short infusion in a concentration of 30 mg/kg bodyweight in a sterile, 1% solution. Application of ALA resulted in the endogenous production of the fluorescent photosensitizer, protoporphyrin IX (PP IX). The Combilight PDD 5133 system served as a light source, permitting the switch from white light mode to blue light mode to excite the PP IX accumulated in the ovarian tissue specimens. By means of blue light illumination, intraperitoneally located red fluorescent lesions, which were suspected to be metastases, underwent a biopsy. In addition, several biopsy specimens were taken from nonfluorescent areas of the peritoneal cavity.

RESULTS

In 13 of 29 patients, ovarian carcinoma was confirmed histologically or cytologically. In 12 of these patients, metastases were visible by red fluorescence. In total, 123 biopsies were performed. Comparison of histologic assessment of the biopsy specimens with the fluorescence detection showed that strong red fluorescence had a sensitivity of 92% for detecting tumor tissue on specimens. In only 2% of all biopsy specimens was endometriosis observed in benign tissue specimens using fluorescence. In four of 13 patients with ovarian carcinoma, lesions were detected under fluorescence, which were not observed under white light illumination.

CONCLUSIONS

Laparoscopic fluorescence detection of endogenous PP IX after intraperitoneal application of ALA may provide a higher sensitivity of finding peritoneal metastases of epithelian ovarian carcinoma compared with conventional laparoscopy. Direct visualization of in vivo fluorescence after ALA application may improve the early detection of intraperitoneal ovarian carcinoma micrometastases. The high tissue selectivity of PP IX accumulation in tumor tissue specimens also offers the opportunity for therapeutic approaches using photodynamic therapy in the future. Cancer 2004. © 2004 American Cancer Society.
Increased expression of collagen XVIII and its prognostic value in nonsmall cell lung carcinoma
Authors: Chang Hao , Iizasa Toshihiko , Shibuya Kiyoshi , Iyoda Akira , Suzuki Makoto , Moriya Yasumitsu , Liu Tian‐Ling , Hiwasa Takaki , Hiroshima Kenzo , Fujisawa Takehiko
Published: March 2004

BACKGROUND

Angiogenesis plays a crucial role in tumor growth and metastasis. Recently, some studies have focused on the angiogenesis inhibitor endostatin. However, the biologic role of the precursor of endostatin, collagen XVIII, in human malignancy is unknown. The purpose of the current study was to evaluate whether the expression of collagen XVIII has additional prognostic value for survival in patients with nonsmall cell lung carcinoma (NSCLC).

METHODS

The authors investigated the expression of collagen XVIII in 221 patients using immunohistochemical methods. To confirm the specificity of the collagen XVIII polyclonal antibody used in the current study and to test the expression of collagen XVIII in human lung carcinoma, Western blot analysis was performed on a panel of human lung carcinoma cell lines.

RESULTS

Collagen XVIII expression was detected in 162 of 221 patients with NSCLC (73%), primarily in the tumor cell cytoplasm. Low collagen XVIII expression levels were found in 75 tumor specimens, while high collagen XVIII expression levels were noted in 87 tumor specimens. The prevalence of positive collagen XVIII expression was greater in T2–4 tumors than in T1 tumors (P = 0.0235). The prognosis for patients with strongly collagen XVIII–positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII–positive or collagen XVIII–negative NSCLC (P = 0.0010). Multivariate analysis indicated that T status, lymph node status, and the overexpression of collagen XVIII were independent prognostic factors.

CONCLUSIONS

The results of the current study indicated that the overexpression of collagen XVIII was associated with NSCLC progression and poor outcome. Thus, collagen XVIII expression may serve as a useful prognostic marker in patients with NSCLC. Cancer 2004. © 2004 American Cancer Society.
Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group
Authors: Bisogno Gianni , Sotti Guido , Nowicki Yohann , Ferrari Andrea , Garaventa Alberto , Zanetti Ilaria , Favre Claudio , Schiavetti Amalia , Tamaro Paolo , Carli Modesto
Published: March 2004

BACKGROUND

Survivors of childhood malignancies have an increased risk of developing second malignant neoplasms (SMN) due to their prior treatment and/or genetic susceptibility. A small proportion of SMNs are soft tissue sarcomas (STS), whose prognosis is generally thought to be poor, though publications on such patients' treatment and outcome is limited.

METHODS

The authors analyzed 25 patients who were registered for the Italian Cooperative Group protocols for pediatric STS from 1979 to 2000. The primary tumor was STS in five patients; Hodgkin disease in five patients; leukemia in four patients; retinoblastoma, neuroblastoma, and Wilms tumor in two patients each; and other tumor types in five patients. SMNs occurred after a median of 8 years (range, 1.9–15.0 years) and included rhabdomyosarcoma (RMS) in 4 patients, malignant peripheral nerve sheath tumor in 4 patients, extraosseous Ewing family tumor (EFT) in 4 patients, leiomyosarcoma in 3 patients, fibrosarcoma in 2 patients, synovial sarcoma in 2 patients, and other tumor types in 6 patients. Treatment generally was administered according to the guidelines for primary STS.

RESULTS

Seven non‐RMS patients with STS underwent surgery alone, whereas 18 patients received chemotherapy and 8 patients received radiotherapy. Retreatment was feasible with acceptable toxicity. Fifteen patients were alive in complete remission of their SMN at the time of last follow‐up. Responses to chemotherapy and survival were satisfactory for patients with tumors such as RMS and EFT. Complete tumor resection was correlated with a favorable prognosis in patients with other types of STS and in patients with postirradiation sarcoma. Two patients developed a third malignancy.

CONCLUSIONS

Although prior treatment may hinder the management of these patients, pediatric STS second malignancies can be cured using the same strategies used for de novo pediatric sarcomas. Long‐term follow‐up is mandatory given the risks of further malignancies and more severe, treatment‐related side effects. Cancer 2004. © 2004 American Cancer Society.
p53 apoptotic pathway molecules are frequently and simultaneously altered in nonsmall cell lung carcinoma
Authors: Mori Shoichi , Ito Genshi , Usami Noriyasu , Yoshioka Hiromu , Ueda Yuichi , Kodama Yoshinori , Takahashi Masahide , Fong Kwun M. , Shimokata Kaoru , Sekido Yoshitaka
Published: March 2004

BACKGROUND

Lung carcinomas show frequent inactivation of the p53 tumor suppressor, which regulates an apoptotic pathway. The objective of the current study was to assess how the p53 apoptotic pathway is altered in nonsmall cell lung carcinoma (NSCLC), especially in tumors without p53 alterations.

METHODS

p53, its upstream regulators (p14ARF and HDM2), and downstream effectors of the apoptotic pathway (BAX and BCL2) were studied in 118 NSCLC specimens. p53 was analyzed by single‐stranded conformation polymorphism analysis covering exons 2–11 and by immunohistochemistry (IHC). p14ARF was analyzed by methylation‐specific polymerase chain reaction and IHC. HDM2 was analyzed using Southern blot analysis and IHC. BAX and BCL2 were analyzed by IHC. Two other upstream regulators that regulate the stability of HDM2, PTEN and HAUSP, also were studied.

RESULTS

Of 118 NSCLC specimens that were analyzed, p53 alterations were detected in 74 tumors (63%), p14ARF inactivation was detected in 53 tumors (45%), and overexpression of HDM2 was found in 31 tumors (26%), including 6 tumors with gene amplification. Although p53 inactivation and HDM2 overexpression were detected simultaneously, HDM2 gene amplification was observed only in tumor specimens without p53 mutations. IHC revealed PTEN down‐regulation in 22 of 88 tumors (25%). HAUSP Northern blot analysis demonstrated several‐fold differences in gene expression that did not correlate with p53 alterations. Of 118 NSCLC specimens, expression of BAX and BCL2 expression were detected in 46 tumors (39%) and 17 tumors (14%), respectively. Finally, ASPP1 and ASPP2, molecules involved in mediating the transcription function of p53, were not found to be aberrantly expressed when tested by Northern blot analysis.

CONCLUSIONS

Overall, two or more p53 pathway components were found to be frequently altered in patients with NSCLC. Greater than 90% of the alterations were due to abnormalities of p53, p14ARF, or HDM2. Therefore, the inactivation of one or more components of the p53 pathway appears to be a prerequisite for the development of most NSCLCs. Cancer 2004. © 2004 American Cancer Society.
Mature results of a phase III randomized trial of bacillus Calmette–Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I–III melanoma (E1673)
Authors: Agarwala Sanjiv S. , Neuberg Donna , Park Yuhyun , Kirkwood John M.
Published: March 2004

BACKGROUND

The local and systemic effects of bacillus Calmette–Guerin (BCG) have been known for decades. To investigate the adjuvant effect of BCG on resected American Joint Committee on Cancer (AJCC) Stage I–III melanoma, the Eastern Cooperative Oncology Group conducted a large trial to study the use of BCG alone or a combination of BCG and dacarbazine between 1974 and 1978.

METHODS

A total of 734 patients were randomized to 4 clinical groups consolidated into 2 cohorts. Cohort I compared BCG with observation and Cohort II compared BCG with a combination of BCG and dacarbazine. The primary end points were survival time and time to disease progression.

RESULTS

Within Cohort I, no statistically significant difference in disease‐free survival (DFS) (P= 0.84) or overall survival (OS) (5‐year survival 67% vs. 62%;P= 0.40) was observed between BCG treatment and observation. Within Cohort II, the addition of dacarbazine to BCG did not improve DFS (P= 0.74) or OS (P= 0.81) compared with BCG alone. Toxicity was mild to moderate in both cohorts. Although toxicity with this agent is mild, the use of BCG is associated with the development of punctate abscesses in greater than two‐thirds of patients treated.

CONCLUSIONS

In what to our knowledge is the largest ever trial to test the role of BCG as adjuvant therapy for melanoma, no benefit for BCG was observed for patients with AJCC Stage I–III disease. The mature results of the current trial projected to 30 years confirmed the negative results of previous smaller studies utilizing this agent. Cancer 2004. © 2004 American Cancer Society.
Stereotactic radiosurgery for multiple brain metastases from breast carcinoma
Authors: Muacevic Alexander , Kreth Friedrich W. , Tonn Jörg‐Christian , Wowra Berndt
Published: March 2004

BACKGROUND

The current study analyzed the feasibility and outcome of stereotactic radiosurgery (SRS) for treatment of brain metastases from breast carcinoma.

METHODS

During an 8‐year period, 151 patients with a combined total of 620 brain metastases from breast carcinoma underwent 197 outpatient SRS procedures. Sixty‐three percent of all patients had multiple brain metastases. The median tumor volume was 2.2 cm3 (range, 0.1–20.9 cm3). The mean prescribed tumor dose was 19 ± 4 grays. Local/distant tumor recurrences were treated with additional radiosurgical therapy for patients with stable systemic disease. All patients were categorized according to the Radiation Therapy Oncology Group classification. Survival time and freedom from local tumor recurrence were analyzed using the Kaplan–Meier method. Prognostic factors were identified using the Cox proportional hazards model.

RESULTS

The overall median survival duration was 10 months after SRS. Ninety‐four percent of patients did not experience local brain tumor recurrence after radiosurgery. In addition, 70.2% of patients did not have disease recurrence in the brain. Most patients died of systemically progressing malignancy. A Karnofsky performance score > 70 and recursive partitioning analysis Class I were related to prolonged survival in the univariate and multivariate analyses. Age, whole‐brain radiotherapy, surgery, number of metastases, chemotherapy, and latency period from diagnosis of the primary tumor to the development of brain metastases did not reach prognostic relevance in the multivariate model. Patients with RPA I, II, and III survived 34.9, 9.1, and 7.9 months, respectively. There was no treatment related permanent morbidity and mortality. The transient morbidity rate was 17%. Sixteen patients exhibited symptomatic transient complications related to treatment.

CONCLUSIONS

The results of the current study indicate that SRS is a feasible treatment concept for selected patients with multiple brain metastases from breast carcinoma. Cancer 2004. © 2004 American Cancer Society.
Sentinel lymph nodes in malignant melanoma
Authors: Abrahamsen Helene Nortvig , Hamilton‐Dutoit Stephen J. , Larsen Jørn , Steiniche Torben
Published: March 2004

BACKGROUND

The optimal technique for sentinel lymph node (SN) assessment in patients with melanoma is controversial. Molecular analysis (reverse transcriptase–polymerase chain reaction) detects significantly greater numbers of SNs with suspected micrometastases (up to 71%) than does routine histopathology (approximately 20%). The authors sought to identify possible reasons for this discrepancy and to determine whether using an extended histopathologic protocol could improve diagnostic precision.

METHODS

Two hundred thirty‐one SNs from 100 consecutive patients with cutaneous melanomas that measured 1–4 mm in thickness were bisected, and half of the lymph node was examined according to an extensive histopathologic protocol involving serial sectioning and immunohistochemical analysis of 3 melanocyte‐associated markers (S‐100, HMB‐45, and Melan‐A).

RESULTS

Lymph node melanocytic lesions were frequent, with micrometastases and benign nevus inclusions (BNI) found in SNs in 28% and 28% of patients, respectively (4 SNs contained both). Melan‐A was the most sensitive immunohistochemical marker and was positive in all BNI‐positive SNs and 97% of micrometastasis‐positive SNs. Although HMB‐45 showed differential labeling in micrometastases compared with BNI (82% vs. 16%), immunohistochemistry could not distinguish between those lesions. Micrometastases were already identified on the first central level in 49% of positive SNs, whereas only 23% of SNs with BNI were diagnosed on the first level.

CONCLUSIONS

Extensive serial sectioning with immunohistochemical analysis substantially increased the histopathologic detection of micrometastases and BNI in melanoma SNs to a level approaching the level reported for molecular techniques. The large number of BNIs represents an important potential source of imprecision (false positivity) in SN assays based on nonmorphologic methods. Cancer 2004. © 2004 American Cancer Society.
Nuclear factor‐KappaB modulation as a therapeutic approach in hematologic malignancies
Authors: Panwalkar Amit , Verstovsek Srdan , Giles Francis
Published: March 2004

Nuclear factor‐kappaB (NF‐κB) is a collective term that refers to a small class of dimeric transcription factors for a number of genes, including growth factors, angiogenesis modulators, cell‐adhesion molecules, and antiapoptotic factors. Although most NF‐κB proteins promote transcription, some act as inactivating or repressive complexes. The most common p50‐RelA (p65) dimer known “specifically” as NF‐κB, is relatively abundant, controls the expression of numerous genes, and exists as an inactive cytoplasmic complex bound to inhibitory proteins of the NF‐κB inhibitor (IκB) family. The inactive NF‐κB‐IκB complex is activated by a variety of stimuli, including proinflammatory cytokines, mitogens, growth factors, and stress‐inducing agents. The release of NF‐κB facilitates its translocation to the nucleus, where it promotes cell survival by initiating the transcription of genes encoding stress‐response enzymes, cell‐adhesion molecules, proinflammatory cytokines, and antiapoptotic proteins. Constitutive activation of NF‐κB in the nucleus is observed in some hematologic disorders. With the recent approval of bortezomib for patients with advanced multiple myeloma, NF‐κB modulation is likely to be a therapeutic endeavor of increasing interest in coming years. Cancer 2004. © 2004 American Cancer Society.
A Phase II trial of vinorelbine tartrate in patients with disseminated malignant melanoma and one prior systemic therapy
Authors: Whitehead Robert P. , Moon James , McCachren S. Spence , Hersh Evan M. , Samlowski Wolfram E. , Beck J. Thaddeus , Tchekmedyian Nerses S. , Sondak Vernon K.
Published: March 2004

BACKGROUND

Single‐agent chemotherapy with dacarbazine continues to be the standard of care for the treatment of metastatic melanoma. However, there is a large population of patients who have failed first‐line therapy and might benefit from additional treatment. In the current study, the authors evaluated the antitumor effects and toxicity of vinorelbine therapy in patients who had failed one prior systemic therapy.

METHODS

Patients were required to have a histologic diagnosis of melanoma and be of Stage IV with measurable disease, a Southwest Oncology Group (SWOG) performance status (PS) of 0–2, no evidence of brain metastases, and adequate bone marrow and liver function. Treatment was comprised of vinorelbine given at a dose of 30 mg/m2/week by intravenous bolus.

RESULTS

Twenty‐four patients were registered to the study, 3 of whom were determined to be ineligible. The 21 eligible patients had a median age of 58 years with a SWOG PS of 0 in 7 patients, 1 in 13 patients, and 2 in 1 patient. There were no complete or partial responses observed, for a response rate of 0 of the 21 patients studied (95% confidence interval [95% CI], 0–16%); the study closed after the first stage of accrual. The estimated median progression‐free survival was 2 months (95% CI, 1.5–3.3 months) and the estimated median overall survival was 6 months (95% CI, 3.7–8.3 months). There was one death due to febrile neutropenia reported, with six patients experiencing one or more Grade 4 toxicities, including neutropenia/granulocytopenia, leukopenia, dyspnea, and fatigue.

CONCLUSIONS

Despite impressive preclinical activity against melanoma, vinorelbine does not appear to have enough clinical activity to be of interest in previously treated patients with disseminated melanoma. The progression‐free and overall survival results noted in previously treated patients in the current study were similar to results reported in prior SWOG Phase II trials in untreated patients. The group of previously treated patients may be used to evaluate new agents for the treatment of disseminated melanoma. Cancer 2004. © 2004 American Cancer Society.
High‐dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma
Authors: Morris Michael J. , Smaletz Oren , Solit David , Kelly W. Kevin , Slovin Susan , Flombaum Carlos , Curley Tracy , Delacruz Anthony , Schwartz Lawrence , Fleisher Martin , Zhu Andrew , Diani Meghan , Fallon Mary , Scher Howard I.
Published: March 2004

BACKGROUND

Preclinical and clinical data have suggested that high‐dose calcitriol (1,25‐dihydroxycholecalciferol) has activity against prostate carcinoma. Pulse‐dosed calcitriol and dexamethasone may maximize tolerability and efficacy. The authors examined the toxicity of pulse‐dosed calcitriol with zoledronate and with the addition of dexamethasone at the time of disease progression.

METHODS

Patients with progressive prostate carcinoma were eligible for the current study. In cohorts of 3–6 patients, calcitriol was administered for 3 consecutive days per week, starting at a dose of 4 μg per day. Doses were escalated to 30 μg per day. Intravenous zoledronate (4 mg) was administered monthly. Dexamethasone could be added to the regimen at disease progression. Toxicities, markers of bone turnover, plasma calcitriol levels, and clinical outcomes were recorded.

RESULTS

Thirty‐one patients were treated in cohorts that were defined by the calcitriol dose administered (4, 6, 8, 10, 14, 20, 24, or 30 μg). Seven patients received dexamethasone. Three patients had their doses reduced due to calcium‐related laboratory findings. Patients tolerated therapy well, even in the 30 μg cohort; therefore, a maximum tolerated dose was not defined. Peak plasma levels observed in the 24 μg and 30 μg cohorts ranged from 391 to 968 pg/mL. Minimal antitumor effects were observed.

CONCLUSIONS

Calcitriol was well tolerated at doses up to and including 30 μg 3 times per week in combination with intravenous zoledronate 4 mg monthly, with or without dexamethasone, in patients with progressive prostate carcinoma. Peak plasma levels in the 24 μg and 30 μg cohorts were greater than the levels associated with antitumor effects preclinically. Due to the cumbersome dosing schedule and the lack of significant activity observed, Phase II trials of this regimen are not planned. Cancer 2004. © 2004 American Cancer Society.
Characterization of FAMPAC, a newly identified human pancreatic carcinoma cell line with a hereditary background
Authors: Eisold Sven , Ryschich Eduard , Linnebacher Michael , Giese Thomas , Nauheimer Dirk , Wild Anja , Bartsch Detlef K. , Büchler Markus W. , Schmidt Jan
Published: March 2004

BACKGROUND

A novel pancreatic carcinoma cell line, FAMPAC, was identified from investigation of poorly differentiated pancreatic adenocarcinoma cells found in a patient with a familial predisposition to pancreatic carcinoma. A gene responsible for familial pancreatic carcinoma has not been identified to date.

METHODS

The FAMPAC cell line was characterized by its morphology, growth rate, tumorigenicity, and chromosomal analysis. Three known tumor suppressor genes, p16/CDKN2, BRCA2, and p53, all of which are important in the development of pancreatic carcinoma and frequently are involved in a variety of cancer syndromes, were analyzed.

RESULTS

FAMPAC cells grew as an adhering monolayer in culture medium supplemented with 10% fetal bovine serum and formed tumors rapidly in nude mice. The doubling time ranged from 24 to 48 hours. Karyotype analysis demonstrated the complexity of chromosomal deletions and rearrangements. The cells were negative for ductal differentiation markers such as cytokeratin 7 and MUC1, indicating poor differentiation. Analysis of FAMPAC cells revealed overexpression of the mutated p53 gene (exon 5, codon 175: CGC → CAC), the presence of a homozygous deletion in the p16 gene, and the presence of wild‐type BRCA2 in the tested hot spots.

CONCLUSIONS

To the authors' knowledge, FAMPAC is the first established human pancreatic carcinoma cell line associated with a familial background. FAMPAC is a tumorigenic cell line with a complex molecular pattern of mutations. These findings may be useful in understanding the mechanisms responsible for the development of sporadic or hereditary forms of pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society.