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Manuel Martinez

Publications and source records attributed to Manuel Martinez.

17 recordsLinked to original sources
PubMed2006

Structural and functional diversity within the cystatin gene family of Hordeum vulgare.

Phytocystatins are inhibitors of cysteine proteinases from plants putatively involved in defence and as endogenous regulators of protein turnover. Seven genes encoding cystatins (HvCPI-1 to HvCPI-7), identified from EST collections and from an endosperm cDNA library, have been characterized. The intron-exon structure of their corresponding ORFs has been determined and the predicted three-dimensional models for the seven barley cystatins have been established, based on the known crystal structure of oryzacystatin I from rice. Only one out of the seven deduced proteins, HvCPI-7, had sequence variations affecting the three conserved motifs implicated in the enzyme-inhibitor interaction. In three cases, HvCPI-5, HvCPI-6, and HvCPI-7, amino acid differences lead to the prediction of important structural changes in their three-dimensional structures. Northern blot analysis indicated that the seven genes have different expression patterns in barley tissues. The recombinant proteins expressed in Escherichia coli showed distinct inhibitory properties in vitro, with different K(i) values, against the three cysteine proteinases tested: papain, cathepsin B, and cathepsin H. Moreover, these recombinant proteins presented differential fungicidal characteristics inhibiting the growth of phytopathogenic fungi Botrytis cinerea and Fusarium oxysporum in vitro. The resulting implications for the structural and functional diversity of the seven barley cystatins studied are discussed.

Amino Acid Motifs↗
PubMed2006

Hypertonic stress increases phosphatidylinositol 4,5-bisphosphate levels by activating PIP5KIbeta.

Hyperosmotic stress increases phosphoinositide levels, reorganizes the actin cytoskeleton, and induces multiple acute and adaptive physiological responses. Here we showed that phosphatidylinositol 4,5-bisphosphate (PIP(2)) level increased rapidly in HeLa cells during hypertonic treatment. Depletion of the human type I phosphatidylinositol 4-phosphate 5-kinase beta isoform (PIP5KIbeta) by RNA interference impaired both the PIP(2) and actin cytoskeletal responses. PIP5KIbeta was recruited to membranes and was activated by hypertonic stress through Ser/Thr dephosphorylation. Calyculin A, a protein phosphatase 1 inhibitor, blocked the hypertonicity-induced PIP5KIbeta dephosphorylation/activation as well as PIP(2) increase in cells. Urea, which raises osmolarity without inducing cell shrinkage, did not promote dephosphorylation nor increase PIP(2) levels. Disruption or stabilization of the actin cytoskeleton, or inhibition of the Rho kinase, did not block the PIP(2) increase nor PIP5KIbeta dephosphorylation. Therefore, PIP5KIbeta is dephosphorylated in a volume-dependent manner by a calyculin A-sensitive protein phosphatase, which is activated upstream of actin remodeling and independently of Rho kinase activation. Our results establish a cause-and-effect relation between PIP5KIbeta dephosphorylation, lipid kinase activation, and PIP(2) increase in cells. This PIP(2) increase can orchestrate multiple downstream responses, including the reorganization of the actin cytoskeleton.

Actins↗
PubMed2006

Lipid raft adhesion receptors and Syk regulate selectin-dependent rolling under flow conditions.

Selectins and their ligand P-selectin glycoprotein ligand-1 (PSGL-1) mediate leukocyte rolling along inflamed vessels. Cell rolling is modulated by selectin interactions with their ligands and by topographic requirements including L-selectin and PSGL-1 clustering on tips of leukocyte microvilli. Lipid rafts are cell membrane microdomains reported to function as signaling platforms. Here, we show that disruption of leukocyte lipid rafts with cholesterol chelating agents depleted raft-associated PSGL-1 and L-selectin and strongly reduced L-, P-, and E-selectin-dependent rolling. Cholesterol repletion reversed inhibition of cell rolling. Importantly, leukocyte rolling on P-selectin induced the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase associated to lipid raft PSGL-1. Furthermore, inhibition of Syk activity or expression, with pharmacologic inhibitors or by RNA interference, strongly reduced leukocyte rolling on P-selectin, but not on E-selectin or PSGL-1. These observations identify novel regulatory mechanisms of leukocyte rolling on selectins with a strong dependency on lipid raft integrity and Syk activity.

Cholesterol↗
PubMed2006

HvMCB1, a R1MYB transcription factor from barley with antagonistic regulatory functions during seed development and germination.

The functional analysis of hydrolase gene promoters induced by gibberellin (GA) in barley aleurone cells upon germination has identified a tripartite GA-response complex (GARC) containing a 5'-TATCCAC-3' box as well as the GA-responsive element (GARE) recognized by GAMYB and the pyrimidine box interacting with the DOF transcription factors BPBF and SAD. We show here that the MCB1 gene encoding a R1MYB protein binds to the 5'-TATCCAC-3' (GATA core) box in vitro and is a transcriptional repressor of a GA-induced amylase (Amy6.4) promoter in bombarded aleurone layers. Northern blot and mRNA in situ hybridization analyses showed that the MCB1 transcripts accumulate in the aleurone cells upon germination, as well as in endosperm tissues during seed development. The HvMCB1 protein expressed in bacteria binds in a specific manner to a 27-mer oligonucleotide containing the 5'-TATCCAC-3' sequence, derived from the promoter region of the Amy6.4 gene. Accumulation of the MCB1 transcript diminished in response to external GA incubation in aleurone cells, and in transient expression experiments HvMCB1 repressed transcription of the Amy6.4 promoter in GA-treated aleurone layers and reversed the GAMYB-mediated activation of this amylase promoter. In contrast, during endosperm maturation HvMCB1 acted as a transcription activator of the seed-specific Itr1 gene promoter through binding to a 5'-GATAAGATA-3' box.

Amino Acid Sequence↗
PubMed2005

The strawberry gene Cyf1 encodes a phytocystatin with antifungal properties.

An EST, encoding a strawberry phytocystatin (PhyCys) obtained from a developing fruit of Fragariaxananassa cv. Elsanta has been characterized. The corresponding gene (Cyf1) had three introns interrupting its ORF that codes for a protein (FaCPI-1) of 235 amino acid residues with a putative signal peptide of 29 residues and an estimated molecular mass for the mature protein of 23.1 kDa. This protein contains, besides a C-terminal extension, several motifs conserved in all members of the PhyCys superfamily: (i) a GG and LARFAV-like motifs towards the N-terminal part of the protein; (ii) the reactive site QVVAG, and (iii) a conserved PW, downstream of the reactive site. Northern blot and in situ hybridization analyses indicated that the Cyf1 gene was expressed in fully expanded leaves, in roots and in achenes, but not in the receptacle (pseudocarp) during fruit development. The recombinant FaCPI-1 protein expressed in E. coli efficiently inhibited papain (K(i) 1.9 x 10(-9) M) and less so cathepsin H (K(i) 4.7 x 10(-7) M) and cathepsin B (K(i) 3.3 x 10(-6) M), and was a good inhibitor of the in vitro growth of phytopathogenic fungi Botrytis cinerea (EC(50): 1.90 microM) and Fusarium oxysporum (EC(50): 2.28 microM).

Amino Acid Sequence↗
PubMed2005

The DOF protein, SAD, interacts with GAMYB in plant nuclei and activates transcription of endosperm-specific genes during barley seed development.

The DOF protein, SAD, previously shown to be a transcriptional activator in barley aleurone cells upon seed germination, also has an important role in gene regulation during endosperm development. mRNA was detected in early (10 days after flowering) developing barley seeds where it accumulated in the starchy endosperm, aleurone cells, nucellar projection, vascular tissues and the immature embryo, as shown by RT-PCR and in situ hybridization analyses. The SAD protein, expressed in bacteria, binds to oligonucleotides containing the prolamine box, 5'-A/TAAAG-3'sequence, derived from the promoter regions of the endosperm-specific genes Hor2 and Itr1, encoding a B-hordein and trypsin-inhibitor BTI-CMe, respectively. SAD competed for the same binding sites with another endosperm-expressed DOF protein, BPBF. Transient expression experiments in co-bombarded developing endosperms demonstrated that SAD trans-activated transcription from Hor2 and Itr1 promoters through binding to the intact DOF motifs. When the two DOF factors are co-bombarded together an additive effect was observed upon the expression of the Itr1 gene. In-frame fusion of the Sad ORF to the reporter green fluorescent protein gene directs the fluorescence expression to the nucleus in transiently transformed onion epidermal layers. The visualization of fluorescence in the nucleus of onion cells, using the bimolecular fluorescent complex (BiFC) approach, has shown the in vivo interaction between SAD and the R2R3MYB protein GAMYB. The interaction in plant cells has also been documented for the DOF protein BPBF and GAMYB, but nuclear interaction could not be detected between BPBF and SAD by this procedure.

Cell Nucleus↗
PubMed2004

Regulation of PSGL-1 interactions with L-selectin, P-selectin, and E-selectin: role of human fucosyltransferase-IV and -VII.

P-selectin glycoprotein ligand-1 (PSGL-1) interactions with selectins regulate leukocyte migration in inflammatory lesions. In mice, selectin ligand activity regulating leukocyte recruitment and lymphocyte homing into lymph nodes results from the sum of unequal contributions of fucosyltransferase (FucT)-IV and FucT-VII, with FucT-VII playing a predominant role. Here we have examined the role of human FucT-IV and -VII in conferring L-selectin, P-selectin, and E-selectin binding activities to PSGL-1. Lewis x (Le(x)) carbohydrate was generated at the CHO(dhfr)(-) cell surface by FucT-IV expression, whereas sialyl Le(x) (sLe(x)) was synthesized by FucT-VII. Both human FucT-IV and -VII had the ability to generate carbohydrate ligands that support L-selectin-, P-selectin-, and E-selectin-dependent rolling on PSGL-1, with FucT-VII playing a major role. Cooperation was observed between FucT-IV and -VII in recruiting L-, P-, or E-selectin-expressing cells on PSGL-1 and in regulating cell rolling velocity and stability. Additional rolling adhesion assays were performed to assess the role of Thr-57-linked core-2 O-glycans in supporting L-selectin-, P-selectin-, and E-selectin-dependent rolling on PSGL-1. These studies confirmed that core-2 O-glycans attached to Thr-57 play a critical role in supporting L- and P-selectin-dependent rolling and revealed that additional binding sites support >75% of E-selectin-mediated rolling. The observations presented here indicate that human FucT-IV and -VII both contribute and cooperate in regulating L-selectin-, P-selectin-, and E-selectin-dependent rolling on PSGL-1, with FucT-VII playing a predominant role in conferring selectin binding activity to PSGL-1.

Animals↗
PubMed2004

Kinetico-mechanistic studies of C-H bond activation on new Pd complexes containing N,N'-chelating ligands.

The hybrid imine/amine palladium(II) coordination complexes [PdX2(kappa2-N(imino),N(amino))](X = Cl, AcO; kappa2-N(imino),N(amino)= 4ClC6H4CHNCH2(CH2)nN(CH3)2, n= 1, 2) have been prepared in different isomeric forms which include E/Z arrangement around the C[double bond]N bond of the hybrid ligand and {Pd(kappa(2)-N(imino),N(amino))} ring conformation. The crystal structures of four of them, E-1AcO, Z-1AcO, E-2AcO and E-2Cl, have been determined and the solution behaviour in acetic acid, the common cyclometallating solvent, for all these systems studied. The complexes in acetic acid solution are shown to maintain the structure determined by X-ray crystallography, as they do in deuterated chloroform. Nevertheless, a partial opening equilibrium of the {Pd(kappa2-N(imino),N(amino))} ring is observed by NMR experiments. When the complexes are held in solution for longer periods the corresponding cyclometallated derivatives, 1AcO-CM, 2AcO-CM, 1Cl-CM and 2Cl-CM, containing the {Pd(kappa2-C,N(imino))} palladacycle are obtained, as characterized by 1H NMR spectroscopy. In these compounds the total opening of the N(amino) moiety of the ligand has occurred. The C-H bond activation process has been studied kinetico-mechanistically at different temperatures, pressures and acid concentrations; the results agree with the need of an opening of the chelate ring in [PdX2(kappa2-N(imino),N(amino))] prior to the proper cyclometallation reaction. The values of the enthalpies of activation are higher than those observed for known N-monodentated cyclometallating ligands, as should correspond to the contribution of a ligand dechelation pre-equilibrium. The entropies and volumes of activation are also indicative of this predissociation that include an important amount of contractive ordering. The presence of small amounts of triflic acid in the reaction medium accelerates the reaction to the value observed for N(imino)-monodentate systems, indicating that the full opening of the chelate ring has taken place. For the badly oriented isomeric forms of the ligand in the chelated complex (Z), the cyclometallation process is even more slow and corresponds directly to the reorganization of the ligand to its cyclopalladation-active (E) conformation.

Journal Article↗
PubMed2004

Tuning the metal-to-metal charge transfer energy of cyano-bridged dinuclear complexes.

The metal-to-metal charge transfer (MMCT) transitions of a series of Class II mixed valence dinuclear complexes bearing cyano bridging ligands may be varied systematically by variations to either the hexacyanometallate(II) donor or Co(III) acceptor moieties. Specifically, the new dinuclear species trans-[L(14S)CoNCFe(CN)(5)](-)(L(14S)= 6-methyl-1,11-diaza-4,8-dithia-cyclotetradecane-6-amine) and trans-[L(14)CoNCRu(CN)(5)](-)(L(14)= 6-methyl-1,4,8,11-tetraazacyclotetradecane-6-amine) have been prepared and their spectroscopic and electrochemical properties are compared with the relative trans-[L(14)CoNCFe(CN)(5)](-). The crystal structures of Na(trans-[L(14S)CoNCFe(CN)(5)]).51/2H(2)O.1/2EtOH, Na(trans-[L(14)CoNCRu(CN)(5)]).3H(2)O and Na(trans-[L(14)CoNCRu(CN)(5)]).8H(2)O are also reported. The ensuing changes to the MMCT energy have been examined within the framework of Hush theory, and it was found that the free energy change between the redox isomers was the dominant effect in altering the energy of the MMCT transition.

Journal Article↗
PubMed2003

Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi.

Phosphatidylinositol 4 phosphate [PI(4)P] is essential for secretion in yeast, but its role in mammalian cells is unclear. Current paradigms propose that PI(4)P acts primarily as a precursor to phosphatidylinositol 4,5 bisphosphate (PIP2), an important plasma membrane regulator. We found that PI(4)P is enriched in the mammalian Golgi, and used RNA interference (RNAi) of PI4KIIalpha, a Golgi resident phosphatidylinositol 4 kinase, to determine whether PI(4)P directly regulates the Golgi. PI4KIIalpha RNAi decreases Golgi PI(4)P, blocks the recruitment of clathrin adaptor AP-1 complexes to the Golgi, and inhibits AP-1-dependent functions. This AP-1 binding defect is rescued by adding back PI(4)P. In addition, purified AP-1 binds PI(4)P, and anti-PI(4)P inhibits the in vitro recruitment of cytosolic AP-1 to normal cellular membranes. We propose that PI4KIIalpha establishes the Golgi's unique lipid-defined organelle identity by generating PI(4)P-rich domains that specify the docking of the AP-1 coat machinery.

Adaptor Protein Complex 1↗
PubMed2003

A single primer pair immunoglobulin polymerase chain reaction assay as a useful tool in fine-needle aspiration biopsy differential diagnosis of lymphoid malignancies.

BACKGROUND: Different polymerase chain reaction (PCR) assays have proved to be useful tools for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements in frozen or paraffin-embedded tissues. However, the usefulness of a single primer pair PCR assay on fine-needle biopsy aspirates has not been proven yet. METHODS: The authors conducted a wide prospective study of 148 lymph nodes and extranodal lymphoid infiltrates obtained by fine-needle aspiration biopsy (FNAB). The power of a single primer pair PCR amplification of the hypervariable CDRIII region IgH genes was evaluated using a pair of consensus primers. The PCR cytologic results were compared with the final clinicopathologic diagnosis of each case assessed by combining cytologic and/or immunophenotypic data and histologic features or clinical follow-up. RESULTS: Among the 139 cases with an evaluable PCR result, 35 of 40 (87%) B-cell non-Hodgkin lymphomas were detected as a monoclonal band. Monoclonal IgH bands also were detected in two of the five (40%) T-cell lymphomas, two of the seven (29%) Hodgkin lymphomas, and 5 of the 87 (6%) reactive lymphoid disorders. These results are similar to those obtained by other authors using seminested PCR or combining different PCR tests in each sample obtained by FNAB or excisional biopsy. CONCLUSIONS: The results of the current study demonstrate the convenience of a single primer pair PCR amplification over seminested methods in terms of lower cost and workload. The existence of PCR false-negative and false-positive results for lymphoma makes it necessary to combine the information obtained by PCR with cytologic and/or immunophenotypic data to optimize the number of lymphoid malignancies correctly diagnosed by FNAB.

Biopsy, Needle↗
PubMed2003

SAD: a new DOF protein from barley that activates transcription of a cathepsin B-like thiol protease gene in the aleurone of germinating seeds.

Functional analysis of hydrolase gene promoters, induced by gibberellin (GA) in aleurone cells following germination, has identified a GA-responsive complex (GARC) as a tripartite element containing a pyrimidine-box motif 5'-CCTTTT-3'. We describe here the characterization of a new barley gene (Sad gene) encoding a transcription factor (SAD) of the DNA binding with One Finger (DOF) class that binds to the pyrimidine box in vitro and activates transcription of a GA-induced protease promoter in bombarded aleurone layers. RT-PCR and in situ hybridization analyses showed that the Sad transcripts accumulated in all tissues analysed, being especially abundant in the scutellum and aleurone cells upon seed germination. The SAD protein, expressed in bacteria, binds in a specific manner to two oligonucleotides containing the sequence 5'-G/CCTTTT/C-3', derived from the promoter region of the Al21 gene encoding a cathepsin B-like cysteine protease. Although the Sad transcript accumulation did not respond to external GA-incubation in aleurone cells, in transient expression experiments in co-bombarded aleurone layers, SAD trans-activated transcription from the Al21 promoter in a similar manner as did GAMYB, a MYB protein previously shown to respond to GA and to activate several hydrolase gene promoters in barley aleurone cells. In vivo interaction between the GAMYB and SAD proteins was shown in the yeast two-hybrid system, where GAMYB potentiates the SAD trans-activation capacity through interaction with its C-terminal domain.

Amino Acid Sequence↗
PubMed2002

Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.

Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating the inflammatory response by mediating leukocyte tethering and rolling on adherent leukocytes. In this study, we have examined the effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding. The functional importance of these modifications was determined by analyzing soluble L-selectin binding and leukocyte rolling on CHO cells expressing various glycoforms of PSGL-1 or mutant PSGL-1 targeted at N-terminal Thr or Tyr residues. Simultaneous expression of core-2 beta1,6-N-acetylglucosaminyltransferase and fucosyltransferase VII was required for optimal L-selectin binding to PSGL-1. Substitution of Thr-57 by Ala but not of Thr-44, strongly decreased L-selectin binding and leukocyte rolling on PSGL-1. Substitution of Tyr by Phe revealed that PSGL-1 Tyr-51 plays a predominant role in mediating L-selectin binding and leukocyte rolling whereas Tyr-48 has a minor role, an observation that contrasts with the pattern seen for the interactions between PSGL-1 and P-selectin where Tyr-48 plays a key role. Molecular modeling analysis of L-selectin and P-selectin interactions with PSGL-1 further supported these observations. Additional experiments showed that core-2 O-glycans attached to Thr-57 were also of critical importance in regulating the velocity and stability of leukocyte rolling. These observations pinpoint the structural characteristics of PSGL-1 that are required for optimal interactions with L-selectin and may be responsible for the specific kinetic and mechanical bond properties of the L-selectin-PSGL-1 adhesion receptor-counterreceptor pair.

Amino Acid Sequence↗
PubMed2002

Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP.

Phosphoinositides have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. Phosphatidylinositol 4-kinases (PtdIns 4-kinases or PI4Ks) are at the apex of the phosphoinsitide cascade. Sequence analysis revealed that mammalian cells contain two type II PtdIns 4-kinase isoforms, now termed PI4KIIalpha and PI4KIIbeta. PI4KIIalpha was cloned first. It is tightly membrane-associated and behaves as an integral membrane protein. In this study, we cloned PI4KIIbeta and compared the two isoforms by monitoring the distribution of endogenous and overexpressed proteins, their modes of association with membranes, their response to growth factor stimulation or Rac-GTP activation, and their kinetic properties. We find that the two kinases have different properties. PI4KIIbeta is primarily cytosolic, and it associates peripherally with plasma membranes, endoplasmic reticulum, and the Golgi. In contrast, PI4KIIalpha is primarily Golgi-associated. Platelet-derived growth factor promotes PI4KIIbeta recruitment to membrane ruffles. This effect is potentially mediated through Rac; overexpression of the constitutively active RacV12 induces membrane ruffling, increases PI4KIIbeta translocation to the plasma membrane, and stimulates its activity. The dominant-negative RacN17 blocks plasma membrane association and inhibits activity. RacV12 does not boost the catalytic activity of PI4KIIalpha further, probably because it is constitutively membrane-bound and already activated. Membrane recruitment is an important mechanism for PI4KIIbeta activation, because microsome-bound PI4KIIbeta is 16 times more active than cytosolic PI4KIIbeta. Membrane-associated PI4KIIbeta is as active as membrane-associated PI4KIIalpha and has essentially identical kinetic properties. We conclude that PI4KIIalpha and PI4KIIbeta may have partially overlapping, but not identical, functions. PI4KIIbeta is activated strongly by membrane association to stimulate phosphatidylinositol 4,5-bisphosphate synthesis at the plasma membrane. These findings provide new insight into how phosphoinositide cascades are propagated in cells.

1-Phosphatidylinositol 4-Kinase↗
PubMed2002

Substitution reactions on cyclometalated Pt(IV) complexes. Associative tuning by fluoro ligands and fluorinated substituents.

The substitution reactions of sulfide by phosphines on Pt(IV) complexes having a cyclometalated imine ligand, two methyl groups in a cis geometrical arrangement, and a halogen and a sulfide as ligands, [Pt (Me)(2)X(C-N)(SR(2))], have been studied as a function of temperature, solvent, and electronic and steric characteristics of the phosphines, sulfides, X, and C-N. In most of these cases, a limiting dissociative mechanism has been found, where the dissociation of the sulfide ligand corresponds to the rate-determining step. The intermediate species formed behaves as a true pentacoordinated Pt(IV) compound in a steady-state concentration only for the systems with SMe(2); for the bulkier SEt(2) and SBzl(2) leaving ligands the rate constants and activation parameters show an important degree of solvent dependence, which correlates with the ability of the solvent to form hydrogen bonds. The X-ray crystal structure of one of the dibenzyl sulfide complexes has been determined, and the geometrical arrangement of the ligands has been determined by NOE NMR measurements at low temperature. The nature of the solvent, imine, sulfide, and halogen ligands produces differences in the reaction rates, which can be quantified very well by the corresponding DeltaS values that move from +48 to -90 J K(-1) mol(-1). The reaction on [Pt(Me)(2)F(C(5)CF(4)CHNCH(2)Ph) (SMe(2))] has been found to take place via a mechanism that depends strongly on the bulkiness of the substituting phosphine. While for PCy(3) the reaction is dissociative, for smaller entering ligands the first associatively activated substitution mechanisms on organometallic Pt(IV) complexes have been established with values of DeltaH and DeltaS in the 28-44 kJ mol(-1) and -120 to -83 J K(-1) mol(-1) ranges. Important intramolecular hydrogen bonding in the starting material can be held responsible for this difference with the remaining systems.

Journal Article↗
PubMedDate not supplied

Docetaxel and carboplatin as first-line therapy in advanced non-small cell lung carcinoma: a phase II study.

BACKGROUND: Taxanes have been widely used against advanced non-small cell lung cancer (NSCLC), alone and in combination with platinum agents. In order to develop a tolerable palliative regimen, we combined carboplatin with low dose docetaxel. PATIENTS AND METHODS: Chemotherapy-naive patients, with Stage IIIB or IV NSCLC and an ECOG performance status < or = 2, were enrolled. Treatment consisted of docetaxel 60 mg/m2 and carboplatin AUC 6 every 21 days. Therapy continued for 1 year or 6 months beyond best response, whichever was greater. RESULTS: Twenty-five patients were enrolled. Most patients (80%) had Stage IV disease. The partial response rate was 16%. Response duration ranged from 6 to 115 weeks. Median survival was 55 weeks. Toxicity was generally limited to grade 3 or 4 neutropenia. There was 1 septic death. CONCLUSION: Survival compared favorably to other similar trials employing higher doses of docetaxel. Additionally, a hematologic toxicity advantage was seen compared to regimens containing higher doses of docetaxel.

Aged↗