bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and in vitro antitumor activity of some triarylantimony di(N‐phenylglycinates)
Authors: Yu Lin , Ma Yong‐Qiang , Wang Guo‐Cang , Li Jin‐Shan 
Published: January 2004

AbstractTriarylantimony(V) di(N‐phenylglycinates) (PhNHCH2COO)2SbAr3 (Ar = Ph, p‐CH3C6H4, p‐ClC6H4, and p‐FC6H4) have been synthesized and characterized by elemental analysis, IR, 1H NMR, and mass spectra. The crystal structure of (PhNHCH2COO)2Sb(C6H4F‐p)3 has been determined by X‐ray diffraction. The in vitro antitumor activities of these compounds against three cancer cell lines are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:32–36, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10208
Bromination of silatranyl‐, germatranyl‐, silyl‐, and germyl‐phenylacetylenes
Authors: Selina Anastasia A. , Karlov Sergey S. , Gauchenova Ekaterina V. , Churakov Andrei V. , Kuz'mina Lyudmila G. , Howard Judith A. K. , Lorberth Jörg , Zaitseva Galina S. 
Published: January 2004

AbstractReactions of element‐substituted alkynes R3MCCPh (R3M = Me3Si, Et3Si, Ph3Si, Et3Ge, n‐Bu3Sn, N(CH2CH2O)3Si, N(CH2CH2O)3Ge, N(CH2‐CHMeO)3Ge, and N(CH2CH2O)2(CH2CHPhO)Ge) with bromine, tetra‐n‐butylammonium tribromide (TBAT), and N‐bromosuccinimide (NBS)/DMSO were investigated. The Z,E‐ratio of isomeric dibromoalkenes formed in bromination reaction with Br2 and TBAT are discussed. The crystal structures of N(CH2CH2O)3SiCCPh and N(CH2CHMeO)3GeX (X = C CPh, C(Br)C(Br)Ph, C(Br2)C(O)Ph), and Ph3SiC(Br)C(Br)Ph are reported. © 2003 Wiley Periodicals, Inc. 15:43–56, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10211
Antimicrobial activity of amino acid, imidazole, and sulfonamide derivatives of pyrazolo[3,4‐d]pyrimidine
Authors: Ghorab M. M. , Ismail Zeinab H. , Abdel‐Gawad Soad M. , Aziem Anhar Abdel 
Published: January 2004

AbstractDerivatives of pyrazolo[3,4‐d]pyrimidine with amino acid 3a–d, imidazole 4a–d, carbonyl 6–9, pyrazole 10, pyrazolone 11, and sulfonamide 12–17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 12, and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b, 3c, 12, and 16 were nearly as active as Terbinafine as positive control. © 2003 Wiley Periodicals, Inc. 15:57–62, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10212
Phenylbiguanide as electron donor in heterocyclic synthesis
Authors: El‐Shaieb Kamal M. , Mourad Aboul‐Fetouh E. , Hassan Alaa A. 
Published: January 2004

AbstractPhenylbiguanide reacts with some π‐acceptors such as TCNE, TCNQ, CNIND, DCNQ, and CHL‐o, if any. opy; 2003 Wiley Periodicals, Inc. Heteroatom Chem 15:63–66, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10213
Synthesis and herbicidal activity of (Z)‐ethoxyethyl 2‐cyano‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylates
Authors: Wang Qing Min , Sun Hui Kai , Huang Run Qiu 
Published: January 2004

Abstract2‐Methylthio‐5‐pyridinemethylene amine was prepared from 2‐chloro‐5‐methylpyridine. Ethoxyethyl 2‐cyano‐3,3‐dimethylthioacrylate was prepared from ethoxyethyl cyanoacetate, carbon disulfide, and dimethyl sulfate in 86.2% yield. Its reaction with 2‐methylthio‐5‐pyridinemethylene amine yielded (Z)‐ethoxyethyl 2‐cyano‐3‐methylthio‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylate. Ethoxyethyl (Z+E)‐2‐cyano‐3‐ethoxyacrylate was synthesized from ethoxyethyl 2‐cyanoacetate and triethyl or‐ thoacetate in 90.7% yield, and its reaction with 2‐ methylthio‐5‐pyridinemethylene amine yielded (Z)‐ethoxyethyl 2‐cyano‐3‐methyl‐3‐(2‐methylthio‐5‐pyri‐dylmethylamino)acrylate. The structures of all of the products were confirmed by 1H NMR, elemental analysis, IR, and mass spectroscopy. The herbicidal activities of the products were evaluated, and the results of bioassay showed that (Z)‐ethoxyethyl 2‐cyano‐3‐methyl‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylate exhibits good herbicidal activity on rape (Brassica napus) at a dose of 1.5 kg/ha. © 2003 Wiley Periodicals, Inc. 15:67–70, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10214
Promotion of 1,3‐dithiolanes using a bentonitic clay as catalyst
Authors: Aceves J. M. , Arroyo G. A. , Vargas Y. M. , Miranda R. , Cabrera A. , Delgado F. 
Published: January 2004

AbstractThe reactions between 1,2‐ethandithiol with several carbonylic compounds to form the corresponding 1,3‐dithiolanes were performed using a natural clay as promotor. The target molecules are used as reagents to obtain fine chemicals, herbicides, fungicides, and pharmaceutical compounds among others applications. A kinetic study of camphorquinone and 1,2‐ethandithiol showed a first‐order dependence with 1,2‐ethandithiol as well as with camphorquinone. The substrate transformation in percent was found to be dependent with the reaction time, the amount of catalyst, and the reagents concentration. © 2003 Wiley Periodicals, Inc. 15:71–76, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10215
Phosphono‐substituted isoindolines and indoles from 2,3‐ and 2,4‐benzoxazin‐1‐ones
Authors: Abdou Wafaa M. , Kamel Azza A. , Khidre Maha D. 
Published: January 2004

AbstractReactions of 2,3‐benzoxazinone 1 and 2,4‐benzoxazinone 2, with trialkyl phosphites 3a–c provide access to new phosphono‐substituted isoindolines 6a–f and indoles 19a–e, respectively. Phosphono‐substituted 2,3‐benzoxazines 5a–c were also obtained in the first reaction. Bisisoindolinylidene (7) was, however, isolated in low yields when 1 was heated with triethyl or triisopropyl phosphite at 100deg;C whereas at 170deg;C 7 was obtained as the major product (∼53%). On the other hand, the reaction of 1 or 2 with dialkyl phosphonates 4a–c proceeded in the presence of aqueous solution of NaOH (5%) to give the respective alkylated product 14a–c or 20a–c. © 2003 Wiley Periodicals, Inc. 15:77–84, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10216
Benzofuranyl‐pyran‐2‐ones, ‐pyridazines, and ‐pyridones from naturally occurring furochromones (visnagin and khellin)
Authors: Keshk Eman M. 
Published: January 2004

AbstractThe novel and versatile enaminones 2a,b were synthesized by treatment of visnaginone methyl ether 1a or khellinone methyl ether 1b with N,N‐dimethylformamide dimethylacetal. They were reacted with hippuric acid or N‐acetylglycine to yield benzofuran‐5‐yl‐2H‐pyran‐2‐ones 3a–d. The reaction of 2a,b with cyanoacetamide and malononitrile dimer in sodium ethoxide gave benzofuran‐5‐yl‐pyridones 4a,b and [benzofuran‐5‐yl‐1H‐pyridine‐2‐ylidene] malononitrile 5a, respectively. Refluxing 2a,b with hydrazine hydrate or with hydroxyla‐ mine afforded benzofuran‐5‐yl‐1H‐pyrazoles 6a,b and benzofuran‐5‐yl‐isoxazoles 7a,b, respectively. Moreover, 2a,b coupled with aryl diazonium salt in the presence of sodium hydroxide to yield 3‐(benzofuran‐5‐yl)‐2‐aryl‐hydrazono‐3‐oxo‐propanals 8a,b which were excellent precursors for the synthesis of pyridazines 9–12. © 2003 Wiley Periodicals, Inc. 15:85–91, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10219
Phenylarsenic(III) complexes of 2‐(2‐hydroxyphenyl)benzothiazolines
Authors: Sharma Simpal , Sharma Rajendra K. , Rai Audhesh K. , Singh Yashpal 
Published: January 2004

AbstractEquimolar reactions of PhAs(OMe)2 (prepared in situ) and 2‐(2‐hydroxyphenyl)benzothiazolines LH2 give the addition products PhAs(OMe)2LH2, while equimolar reactions of PhAsCl2 with Na2L yield substitution products PhAsL. All these derivatives have been characterized by elemental analyses and their plausible structures have been established on the basis of physico‐chemical, IR, and NMR (1H and 13C) spectral studies. © 2003 Wiley Periodicals, Inc. 15:92–96, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.10220
Pathophysiology of acute graft‐versus‐host disease
Authors: Reddy Pavan 
Published: January 2004

AbstractGraft‐versus‐host disease (GVHD) has been the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). The pathophysiology of acute GVHD is complex and can be conceptualized to be a three‐step process based on murine studies. In step 1, the conditioning regimen leads to the damage and activation of host tissues and induces the secretion of inflammatory cytokines. As a consequence, the expression of MHC antigens and adhesion molecules is increased enhancing the recognition of host alloantigens by donor T cells. Donor T‐cell activation in step 2 is characterized by donor T cell interaction with host APCs and subsequent proliferation, differentiation and secretion of cytokines. Cytokines such as IL‐2 and IFN‐γ enhance T‐cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses and prime additional mononuclear phagocytes to produce TNF‐α and IL‐1. These inflammatory cytokines in turn stimulate production of inflammatory chemokines, thus recruiting effector cells into target organs. In step 3, effector functions of mononuclear phagocytes are triggered via a secondary signal provided by lipopolysaccaride (LPS) that leaks through the intestinal mucosa damaged during step 1. This mechanism may result in the amplification of local tissue injury and further promotion of an inflammatory response, which, together with the CTL and NK components, leads to target tissue destruction in the transplant host. The following review discusses the three‐step process of the pathophysiology of experimental acute GVHD. Copyright © 2003 John Wiley & Sons, Ltd.
Low dose 2‐CdA schedule activity in splenic marginal zone lymphomas
Authors: Riccioni R. , Caracciolo F. , Galimberti S. , Cecconi N. , Petrini M. 
Published: January 2004

AbstractSplenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second‐line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m2/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression‐free‐survival was achieved by 37% with a median time of progression‐free‐survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy. Copyright © 2003 John Wiley & Sons, Ltd.
Epoetin alfa corrects anemia and improves quality of life in patients with hematologic malignancies receiving non‐platinum chemotherapy
Authors: Littlewood Timothy J. , Nortier Johan , Rapoport Bernardo , Pawlicki Marek , De Wasch Gilbert , Vercammen Els , Schuette Wolfgang , Wils Jacques , Freund Mathias 
Published: January 2004

AbstractAnemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non‐platinum‐based chemotherapy who were enrolled in a multinational, randomized (2:1), double‐blind, placebo‐controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb ≥2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached ≥12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan–Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan–Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer‐ and anemia‐specific QOL domains evaluated. Although the study was not powered for survival, Kaplan–Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non‐platinum chemotherapy for hematologic malignancies. Copyright © 2004 John Wiley & Sons, Ltd.
Glutathione S‐transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers
Authors: Sikdar Nilabja , Paul Ranjan Rashmi , Roy Bidyut 
Published: January 2004

AbstractPolymorphism in glutathione S‐transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case‐control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction‐restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val‐ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0–2.0) and lower (OR = 1.4; 95% CI = 1.0–1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0–4.0; OR = 2.0, 95% CI = 1.0–4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing‐year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0–9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack‐year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0–5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals. © 2003 Wiley‐Liss, Inc.
Parvovirus H‐1 infection of human glioma cells leads to complete viral replication and efficient cell killing
Authors: Herrero y Calle Marta , Cornelis Jan J. , Herold‐Mende Christel , Rommelaere Jean , Schlehofer Joerg R. , Geletneky Karsten 
Published: January 2004

AbstractThe extremely poor prognosis of malignant gliomas requires the investigation of other than standard therapies, i.e., the application of oncolytic viruses. In our study, we evaluated the effects of the oncosuppressive parvovirus H‐1 on different established glioblastoma cell lines of rat and human origin and on short‐term/low‐passage cultures of human glioblastoma cells. We observed an efficient and dose‐dependent killing of all glioma cell cultures at low multiplicities of infectious particles (MOI) per cell. Southern blot analysis of viral DNA amplification, RT‐PCR analysis of viral RNA expression and Western blot analysis of the expression of viral structural (VP‐1/VP‐2) and nonstructural (NS‐1) proteins demonstrated the biosynthesis of these viral macromolecular components in all of the cultures. Moreover, all the glioma cells were proficient for the production of infectious H‐1 virus particles. The amount of virus production differed between a several fold increase of the input virus titer in most of the short‐term/low‐passage cultures up to 1,000‐fold in one short‐term glioma and in the rat cells. Glioma cells lines and, more importantly, short‐term/low‐passage cultures of human glioblastomas were found to be highly susceptible target cells for H‐1 virus mediated cytotoxicity. The formation of fully infectious progeny particles in infected glioma cells offers the chance for the induction of secondary rounds of infection resulting in an advanced cytotoxic effect. These advantageous characteristics of H‐1 virus infection of glioma cells, combined with the known low toxicity of H‐1 virus in nontransformed cells, make parvovirus H‐1 a promising candidate for oncolytic glioma therapy. © 2003 Wiley‐Liss, Inc.
Potent effect of 5‐HPBR, a butanoate derivative of 4‐HPR, on cell growth and apoptosis in cancer cells
Authors: Han Hye‐Sook , Kwon Youn‐Ja , Park Si‐Ho , Kim Eun‐Joo , Rho Young‐Soy , Sin Hong‐Sig , Um Soo‐Jong 
Published: January 2004

AbstractFenretinide, 4‐(N‐hydroxyphenyl) retinamide (4‐HPR), has demonstrated anticancer activity associated with a favorable toxicity profile and is now being investigated in several clinical trials. However, its plasma levels in patients have been far lower than the effective concentration required to induce apoptosis (usually 10 μM). This result has led to the synthesis of derivatives with better efficacy. Sodium butyrate's potential as an anticancer agent prompted us to synthesize a butanoate derivative of 4‐HPR, 5‐hydroxyphenyl butanoate retinamide (5‐HPBR) and compare it to the parent compound for antitumor potential in vitro. The cytotoxicity of 5‐HPBR was 2‐ to 6‐fold greater than that of 4‐HPR against cancer cell lines derived from various tissues. In premalignant bronchial cells (BEAS2B), 5‐HPBR exhibited about a 10‐fold stronger cytotoxicity than did 4‐HPR. Normal CHANG liver cells were unaffected by either 4‐HPR or 5‐HPBR. Subsequent assays using DNA fragmentation, DAPI staining, FACS and Western blotting suggested that the potent inhibitory effect of 5‐HPBR is mediated by apoptosis; the exact mechanism appears to differ among cancer cell types. In transcription assays with COS‐1 cells, 5‐HPBR selectively activated RARβ and RARγ but was a weaker ligand for all 3 subtypes of RAR than either all‐trans retinoic acid or 4‐HPR. Overall, these data suggest that 4‐BHPR may be a promising retinoid with enhanced antitumor activity and reduced toxicity. © 2003 Wiley‐Liss, Inc.
Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin
Authors: Fang Jun , Sawa Tomohiro , Akaike Takaaki , Greish Khaled , Maeda Hiroshi 
Published: January 2004

AbstractHeme oxygenase‐1 (HO‐1), an inducible enzyme that catalyzes oxidative degradation of heme to form biliverdin, carbon monoxide and free iron, may protect tumor cells against oxidative stress, thus contributing to rapid tumor growth in vivo. Here, we discuss whether pegylated zinc protoporphyrin (PEG‐ZnPP), a potent HO inhibitor, modulates the chemotherapeutic response of tumor cells to treatment that generates reactive oxygen species (ROS). PEG‐ZnPP is a water‐soluble HO inhibitor that accumulates in tumor tissues after intravenous administration. Cytotoxicity of antitumor agents in vitro was determined by means of MTT and annexin V assays using human colon carcinoma SW480 cells. Mice bearing sarcoma 180 tumors were used as an in vivo model. Pegylated D‐amino acid oxidase (PEG‐DAO), which behaves as an oxidative chemotherapeutic agent by generating toxic oxidants at tumor tissues, was administered with its substrate D‐proline to mice with or without PEG‐ZnPP pretreatment. PEG‐ZnPP‐treated SW480 cells became vulnerable to insults caused by various cytotoxic agents; the 50% lethal doses were reduced by 25%, 39%, 83%, and 61% for hydrogen peroxide, t‐butyl hydroperoxide, camptothecin and doxorubicin, respectively. Cells treated with PEG‐ZnPP plus cytotoxic oxidants exhibited marked production of intracellular ROS, which paralleled the incidence of apoptosis. PEG‐ZnPP pretreatment significantly reduced tumor growth in mice receiving PEG‐DAO/D‐proline compared to no PEG‐ZnPP pretreatment. These findings suggest that HO‐1 may become an attractive target for chemotherapeutic intervention. Further study of the effect of PEG‐ZnPP plus conventional anticancer drugs that generate ROS, such as cisplatin, camptothecin, doxorubicin, mitomycin C and etoposide, is warranted. © 2003 Wiley‐Liss, Inc.
Targeting and amplification of immune killing of tumor cells by pro‐Smac
Authors: Li Rui , Rüttinger Dominik , Urba Walter , Fox Bernard A. , Hu Hong‐Ming 
Published: January 2004

AbstractOverexpression of inhibitors of apoptosis (IAP) is one potential mechanism for tumor cells to evade immune surveillance. To determine whether immune‐mediated killing of tumor cells can be enhanced by neutralization of IAP proteins, 2 novel eGFP‐Smac fusion proteins (pro‐Smac) were introduced into the poorly immunogenic mouse melanoma cell line, B16BL6‐D5 (D5). Each fusion protein contained Smac and a cleavage site specific for granzyme B (GrB) or caspase 8, thereby targeting the 2 major killing mechanisms of cytotoxic T‐lymphocyte (CTL) and NK cells. Expression of a pro‐Smac fusion protein by D5 tumor cells greatly enhanced the susceptibility to killing by lymphokine‐activated killer (LAK) cells or purified GrB. GrB‐mediated killing was increased to a much greater extent when tumor cells expressed the eGFP‐Smac fusion protein with a GrB cleavage site compared to a caspase 8 cleavage site. In contrast, perforin‐deficient LAK cells, which lack GrB‐mediated cytotoxicity but process normal ligands for death receptors, killed D5 tumor cells expressed pro‐Smac with caspase 8 cleavage site more efficiently. Enhanced killing by GrB was also accompanied by processing of the fusion protein and increased caspase‐3‐like activity. These results indicate that killing of tumor cells can be amplified by targeting cell‐mediated cytotoxic mechanisms via expression of pro‐Smac fusion proteins. © 2003 Wiley‐Liss, Inc.