bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly combination chemotherapy with docetaxel and gemcitabine as first‐line treatment for elderly patients and patients with poor performance status who have extensive‐stage small cell lung carcinoma
Authors: Hainsworth John D. , Carrell Donna , Drengler Ronald L. , Scroggin Carroll , Greco F. Anthony 
Published: May 2004

AbstractBACKGROUNDThe goal of the current study was to evaluate the feasibility, toxicity, and efficacy of a novel combination of weekly docetaxel and gemcitabine for elderly patients and patients with poor performance status who had advanced‐stage small cell lung carcinoma (SCLC).METHODSPreviously untreated patients with advanced‐stage SCLC were eligible for the current clinical trial. In addition, patients were required to be age > 65 years or to have poor performance status (Eastern Cooperative Oncology Group 2). All patients received 800 mg/m2 gemcitabine and 30 mg/m2 docetaxel intravenously on Days 1, 8, and 15. Courses were repeated at 28‐day intervals.RESULTSForty patients were enrolled in the current multicenter, community‐based trial. Nine patients (23%) had partial responses to treatment. The median survival for the entire group was 4 months. Fourteen percent of patients were alive at 1 year. Myelosuppression was mild to moderate, with no episodes of neutropenia and fever. Grade 3/4 fatigue (25%) was the only common nonhematologic toxicity.CONCLUSIONSAlthough relatively well tolerated, the weekly regimen of gemcitabine and docetaxel possessed only modest activity in this group of patients with unfavorable prognosis. The regimen offered no potential advantages over standard treatment approaches and is not recommended for further development. Cancer 2004. © 2004 American Cancer Society.
Preoperative induction of CPT‐11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction
Authors: Ajani Jaffer A. , Walsh Garrett , Komaki Ritsuko , Morris Jeff , Swisher Stephen G. , Putnam Joe B. , Lynch Patrick M. , Wu Tsung‐Teh , Smythe Roy , Vaporciyan Ara , Faust Josephine , Cohen Deborah S. , Nivers Rebecca , Roth Jack A. 
Published: May 2004

AbstractBACKGROUNDPatients with localized esophageal carcinoma often develop locoregional and distant disease recurrence. The current study investigated the outcome of a new chemotherapy combination as induction therapy before chemoradiotherapy.METHODSForty‐three patients with resectable carcinoma of the esophagus or gastroesophageal junction were enrolled. Most of the tumors were endoscopic ultrasonography (EUS) EUST3 (84%) and EUSN1 (63%). The patients received ≤ 2 6‐week cycles of CPT‐11 and cisplatin followed by chemoradiotherapy (45 grays with 5‐fluorouracil and paclitaxel). Five to six weeks after chemoradiotherapy, the patients underwent staging and surgery. The feasibility, curative resection rates, overall and disease‐free survival rates, rate of significant pathologic response, and patterns of disease recurrence were assessed.RESULTSOf the 43 patients, 39 (91%) underwent an R0 resection. Two patients (5%) died after surgery. A pathologic complete response (pathCR) was observed in 11 (28%) of the 39 patients (or 26% of the 43 patients). In addition, 16 patients (41% of 39 patients or 37% of 43 patients) had < 10% viable tumor in the surgical specimen (pathPR). A comparison of endoscopic ultrasonograpy T and N classifications with surgical T and N classifications demonstrated significant down‐staging (P < 0.01). The median survival period of all 43 patients was 22.1 months. Patients who had achieved a pathCR or pathPR had a longer median survival (25.6 months) than those who achieved less than a pathPR (18.5 months; P = 0.52). None of the clinical parameters examined were found to correlate with survival or pathologic response.CONCLUSIONSCPT‐11–based induction chemotherapy resulted in substantial pathCR and pathPR rates, both of which lead to a favorable survival outcome. The three‐step strategy needs to be developed further, with the investigation of targeted therapies with chemotherapy and radiotherapy. Cancer 2004. © 2004 American Cancer Society.
Erythropoietin is effective in improving the anemia induced by imatinib mesylate therapy in patients with chronic myeloid leukemia in chronic phase
Authors: Cortes Jorge , O'Brien Susan , Quintas Alfonso , Giles Francis , Shan Jianquin , Rios Mary Beth , Talpaz Moshe , Kantarjian Hagop 
Published: May 2004

AbstractBACKGROUNDMyelosuppression occurs in up to 50% of patients with chronic myeloid leukemia (CML) who are treated with imatinib and ≥ Grade 3 myelosuppression is reported in approximately 10% of patients.METHODSThe authors investigated the prognostic significance of anemia occurring during therapy with imatinib in patients with CML in chronic phase.RESULTSOf 338 patients treated with imatinib (150 patients after interferon failure and 188 patients with newly diagnosed CML), 230 (68%) developed anemia. In a multivariate analysis, factors associated with an increased probability of developing anemia were a starting hemoglobin level < 12 g/dL, age ≥ 60 years, female gender, higher imatinib dose, and intermediate or high Sokal risk group. Of these 230 patients, 102 patients received treatment with 40,000 U of recombinant human erythropoietin administered subcutaneously once weekly. An increase in the hemoglobin level of ≥ 2 g/dL was achieved in 69 patients (68%) and 22 patients (22%) had an increase of 1–1.9 g/dL. Patients who developed anemia had a trend toward a lower probability of complete cytogenetic remission compared with patients without anemia (68% vs. 77%;P= 0.14), as well as a trend for inferior survival. Patients with anemia and other manifestations of myelosuppression were found to have a significantly worse outcome than those with isolated anemia.CONCLUSIONSThe authors concluded that erythropoietin is safe and effective in patients in chronic‐phase CML who develop anemia with imatinib therapy. Cancer 2004. © 2004 American Cancer Society.
Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression
Authors: Mhawech Paulette , Greloz Vincent , Oppikofer Chantal , Szalay‐Quinodoz Idliko , Herrmann Francois 
Published: May 2004

AbstractBACKGROUNDCell cycle proteins are important markers in predicting tumor behavior in urothelial carcinoma of the bladder. The objectives of this study were 1) to determine the expression levels of some of those markers in a series of patients with bladder carcinoma, 2) to define their value in distinguishing T1a (minimally invasive) from T1b (invasive) tumors, and 3) to evaluate their use as predictive factors in the progression of T1a and T1b tumors.METHODSTumor specimens from 101 patients were included (22 Ta specimens, 34 T1a specimens, 15 T1b specimens, and 30 T2 specimens). A tissue microarray from the 101 paraffin embedded tissue blocks was constructed. Immunohistochemistry for p16, p27, p21, p53, cyclin D1, and Ki‐67 were performed. To evaluate T1a and T1b tumor progression, clinical and follow‐up data were available for all 49 patients.RESULTSCyclin D1 and p27 were the only markers that showed a significant association with tumor stage and tumor grade (cyclin D1: P = 0.002 and P > 0.00, respectively; p27: P = 0.024 and P = 0.031, respectively). The results indicated that a combination of p21 (odds ratio, 5.7; 95% confidence interval [95% CI], 1.3–24.8 [P = 0.022]) and p16 (odds ratio, 3.7; 95% CI, 0.8–16.5 [P = 0.081]) may have potential use in distinguishing T1b tumors from T1a tumors. Finally, none of the markers examined were found to have predictive value for T1a and T1b tumor progression.CONCLUSIONSThe expression of cyclin D1 and p27 was associated with the most important prognostic factors (tumor stage and grade). The combination of p21 and p16 may have value in distinguishing T1b tumors from T1a tumors, although this finding must be evaluated in much larger series. Finally, none of the markers studied appeared to have predictive value for disease progression in patients with T1a and T1b urothelial bladder tumors. Cancer 2004. © 2004 American Cancer Society.
DFT Calculations on the C−Cl/Si−H Exchange Catalyzed by P,N‐Chelated PtII Complexes
Authors: Sturmayr Dietmar , Schubert Ulrich 
Published: May 2004

AbstractThe mechanism of the previously reported C−Cl/Si−H exchange reaction between HxCCl4−x (x = 0−3) and HSiMe2Ph catalyzed by [PtMeCl(Ph2PCH2CH2NMe2‐κ2P,N)] [PtMeCl(P∩N)] was investigated by DFT calculations. The energetically less‐favored isomer of [PtMeCl(P∩N)], with Cl and P being cis, was identified to be the actual catalytic species. The catalytic reaction proceeds by oxidative addition of the silane, de‐coordination of the nitrogen atom of the P,N‐chelating ligand, reductive elimination of the chlorosilane and oxidative addition of the C−Cl bond of HxCCl4−x. The final step is the reductive elimination of the C−H bond with concomitant re‐coordination of the nitrogen atom of the P,N‐chelating ligand. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Characterization and Applications of a Bismuth Bulk Electrode
Authors: Pauliukaitė Rasa , Hočevar Samo B. , Ogorevc Božidar , Wang Joseph 
Published: May 2004

AbstractA bismuth bulk electrode (BiBE), a new solid‐state electrode, is presented. The polycrystalline metal bismuth disk‐shaped electrode was examined for its anodic stripping voltammetry performance, which was found to be well comparable to that achieved with the bismuth or mercury film electrodes. Useful potential windows of the BiBE in aqueous solutions of pH 1 to 13 were found to range from approximately −1.7 to −0.1 V, depending on pH, where either hydrogen evolution or anodic dissolution of metallic bismuth limit the electrochemical inertness of the BiBE. Employing cyclic voltammetry (CV), the cathodic behavior of the BiBE was examined by testing inorganic (cadmium(II) ions) and organic (2‐nitrophenol) model compounds; a CV quasi‐reversible behavior was recorded in the case of the Cd(II)‐Cd(0) couple. The characteristics of the BiBE under anodic conditions, i.e., at bismuth surface coated with a thin conductive Bi2O3 film, was examined by testing two well‐established redox systems, potassium hexacyanoferate(III) and ruthenium(III) hexaaminechloride; a nearly reversible behavior was recorded in the latter case. Based on the presented preliminary results, BiBE can be considered as an interesting alternative to common solid and (toxic) mercury electrodes for possible use in electrochemical studies and electroanalytical applications.
Genomic aberrations in carcinomas of the uterine corpus
Authors: Micci Francesca , Teixeira Manuel R. , Haugom Lisbeth , Kristensen Gunnar , Abeler Vera M. , Heim Sverre 
Published: May 2004

AbstractEndometrial carcinoma, the most common invasive neoplasm of the female genital tract, occurs either in a hormone‐related, less virulent form (type I) or in a hormone‐independent, more aggressive form (type II). Another cancer of the uterine corpus is carcinosarcoma, a biphasic or mixed epithelial–mesenchymal tumor, now classified as metaplastic carcinoma. We examined by karyotyping and comparative genomic hybridization a consecutive series of 67 endometrial carcinomas and 15 carcinosarcomas and compared the cytogenetic features of the different carcinoma subtypes. All three subtypes of uterine carcinoma had in common a nonrandom gain of material from 1q and 8q but differed from one another in other respects. Endometrial carcinomas of type I mostly presented gains from chromosome arms 1q and 8q and losses from Xp, 9p, 9q, 17p, 19p, and 19q, whereas endometrial carcinomas of type II showed a more complex imbalance picture, with gains from chromosome arms 1q, 2p, 3q, 5p, 6p, 7p, 8q, 10q, and 20q and losses from Xq, 5q, and 17p. The carcinosarcomas mostly showed gains of or from 1q, 5p, 8q, and 12q but losses from 9q, that is, they were much more similar to endometrial carcinomas in their pattern of acquired genomic changes than to sarcomas of the uterine corpus. It was also possible to identify different copy number changes among the different grades of type I carcinomas, between serous papillary and clear‐cell carcinomas of type II, as well as between homologous and heterologous carcinosarcomas. Specifically, type I adenocarcinomas that were highly differentiated mostly showed gains from 1q and 10p; those that were moderately differentiated showed gains from 1q, 7p, 7q, and 10q as well as losses from Xp, 9p, 9q, 17p, 19p, and 19q; whereas those poorly differentiated showed gains from 1q, 2p, 2q, 3q, 6p, 8q, and 20q but losses from Xp, Xq, 5q, 9p, 9q, 17p, and 17q. The serous papillary carcinomas showed gains from 1q, 2p, 2q, 3q, 5p, 6p, 6q, 7p, 8q, 18q, 20p, and 20q but losses from 17p, whereas the clear‐cell carcinomas showed gains from 3q, 7p, 8q, 10q, 16p, and 20q but losses from 6q. Finally, the homologous carcinosarcomas presented gains from 1p, 1q, 8q, 12q, and 17q as well as losses from 9q and 13q, whereas the heterologous tumors showed gains from 1q, 8p, and 8q. The reproducibility of the observed correlations between karyotypic aberration patterns and histological differentiation was underscored by the fact that those carcinosarcomas whose epithelial component resembled type I endometrial carcinomas also exhibiting a type I aberration profile, whereas carcinosarcomas with a type II carcinoma differentiation had karyotypic abnormalities similar to those of type II endometrial carcinomas. © 2004 Wiley‐Liss, Inc.
HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1
Authors: Raevaara Tiina E. , Gerdes Anne‐Marie , Lönnqvist Karin E. , Tybjærg‐Hansen Anne , Abdel‐Rahman Wael M. , Kariola Reetta , Peltomäki Päivi , Nyström‐Lahti Minna 
Published: May 2004

AbstractHeterozygous germ‐line mutations in DNA mismatch repair (MMR) genes predispose individuals to hereditary nonpolyposis colorectal cancer (HNPCC), whereas with homozygous MMR gene mutations children are diagnosed at an early age with de novo neurofibromatosis type 1 (NF1) and/or hematological malignancies. Here, we describe a mutation, MLH1 P648S, which was found in a typical HNPCC family, with one homozygous child displaying mild features of NF1 and no hematological cancers. To evaluate the pathogenicity of the mutation, we studied both the expression and the function of the mutated protein. It generally has been assumed that the predisposing mutations prevent the production of a functional protein. The mutated MLH1 P648S protein was found to be unstable but still functional in mismatch repair, suggesting that the cancer susceptibility in the family and possibly also the mild disease phenotype in the homozygous individual are linked to shortage of the functional protein. © 2004 Wiley‐Liss, Inc.
Maximum‐likelihood estimation of haplotype frequencies in nuclear families
Authors: Becker Tim , Knapp Michael 
Published: May 2004

AbstractThe importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction techniques and many implementations of the expectation‐maximization (EM) algorithm for haplotype frequency estimation exist. Recent research work has shown that incorporating available genotype information of related individuals largely increases the precision of haplotype frequency estimates. We, therefore, implemented a highly flexible program written in C, called FAMHAP, which calculates maximum likelihood estimates (MLEs) of haplotype frequencies from general nuclear families with an arbitrary number of children via the EM‐algorithm for up to 20 SNPs. For more loci, we have implemented a locus‐iterative mode of the EM‐algorithm, which gives reliable approximations of the MLEs for up to 63 SNP loci, or less when multi‐allelic markers are incorporated into the analysis. Missing genotypes can be handled as well. The program is able to distinguish cases (haplotypes transmitted to the first affected child of a family) from pseudo‐controls (non‐transmitted haplotypes with respect to the child). We tested the performance of FAMHAP and the accuracy of the obtained haplotype frequencies on a variety of simulated data sets. The implementation proved to work well when many markers were considered and no significant differences between the estimates obtained with the usual EM‐algorithm and those obtained in its locus‐iterative mode were observed. We conclude from the simulations that the accuracy of haplotype frequency estimation and reconstruction in nuclear families is very reliable in general and robust against missing genotypes. © 2004 Wiley‐Liss, Inc.
Response of heterograft heart valve biomaterials to moderate cyclic loading
Authors: Sun Wei , Sacks Michael , Fulchiero Gregory , Lovekamp Joshua , Vyavahare Naren , Scott Michael 
Published: May 2004

AbstractWe have recently demonstrated that noncalcific tissue damage can lead to significant collagen degradation in clinically explanted bioprosthetic heart valves (BHVs). In the present study we quantified the early response of glutaraldehyde treated bovine pericardium (GLBP) to cyclic tensile loading to begin to elucidate the mechanisms of noncalcific tissue degeneration in BHV biomaterials. GLBP specimens were cycled at 30 Hz to a maximum uniaxial strain of 16% (corresponding to approximately 1‐MPa peak stress), with the loading direction parallel to the preferred collagen fiber (PD) direction. After 30 × 106 cycles, specimens were subjected to biaxial mechanical testing, then cycled until 65 × 106 cycles. The results indicated a permanent change in the unloaded tissue dimensions of +7.1% strain in the PD direction and −7.7% strain in the cross fiber direction (XD) after 65 × 106 cycles and an increase of the collagen crimp period from 40.6 to 45.2 μm by 65 × 106 cycles (p = 0.05). Fourier transform IR spectroscopy analysis indicated that cyclic fatigue of GLBP leads to both collagen conformational changes and early denaturation. Furthermore, no significant changes in areal strain were found under 1‐MPa equibiaxial stress, indicating that cyclic loading changed the collagen fiber orientation but not the overall tissue compliance. These observations suggest that while deterioration of collagen begins immediately, fiber straightening and reorientation dominates the changes in the mechanical behavior up to 65 × 106 cycles. The present study underscores the complexity of the response of biologically derived biomaterials to cyclic mechanical loading. Improved understanding of these phenomena can potentially guide the development of novel chemical treatment methods that seek to improve BHV durability by minimizing these degenerative processes. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 658–669, 2004
A molecular modeling study of the effect of surface chemistry on the adsorption of a fibronectin fragment spanning the 7–10th type III repeats
Authors: Wilson Kerry , Stuart Steven J. , Garcia Andrés , Latour Robert A. 
Published: May 2004

AbstractAlthough it is well documented that proteins adsorb onto biomaterial surfaces, relatively little is quantitatively understood about the effects of adsorption on protein orientation and conformation. Because this is the primary determining factor of protein bioactivity, the ability to accurately predict a protein's orientation and conformation following adsorption will be essential for the rational design of biomaterial surfaces to control biological responses. Force field‐based computational chemistry methods provide an excellent means to theoretically address this issue, with the nontrivial requirement that the force field must be tailored to appropriately represent protein adsorption behavior. Accordingly, we have modified an existing force field (CHARMm) based on semiempirical quantum‐mechanical peptide adsorption data to enable it to simulate protein adsorption behavior in an implicit aqueous environment. This modified force field was then applied to predict the adsorption behavior of the 7–10 type III repeats of fibronectin on functionalized surfaces. Predicted changes in adsorption energy and adsorption‐induced conformation as a function of surface chemistry were found to correlate well with experimentally observed trends for these same systems. This work represents a first attempt towards the development of a molecular mechanics force field that is specifically parameterized to accurately simulate protein adsorption to biomaterial surfaces. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 686–698, 2004
Genetics and cell biology of lysophosphatidic acid receptor‐mediated signaling during cortical neurogenesis
Authors: Kingsbury M.A. , Rehen S.K. , Ye X. , Chun J. 
Published: May 2004

AbstractLysophosphatidic acid (LPA) is a small lysophospholipid that signals through G‐protein coupled receptors (GPCRs) to mediate diverse cellular responses. Two LPA receptors, LPA1 and LPA2, show gene expression profiles in mouse embryonic cerebral cortex, suggesting roles for LPA signaling in cerebral cortical development. Here, we review loss‐of‐function and gain‐of‐function models that have been used to examine LPA signaling. Genetic deletion of lpa1 or both lpa1 and lpa2 in mice results in 50–65% neonatal lethality, but not obvious cortical phenotypes in survivors, suggesting that compensatory signaling systems exist for regulating cortical development. A gain‐of‐function model, approached by increasing receptor activation through exogenous delivery of LPA, shows that LPA signaling regulates cerebral cortical growth and anatomy by affecting proliferation, differentiation and cell survival during embryonic development. © 2004 Wiley‐Liss, Inc.
ERM proteins of the lens
Authors: Bagchi M. , Katar M. , Lo W.‐K. , Yost R. , Hill C. , Maisel H. 
Published: May 2004

AbstractEzrin and radixin and protein 4.1 were detected in the lens of the eye. These proteins were mainly present in the young elongating cortical fiber cells and localized to the plasma membranes. Moesin was not detected. Ezrin, radixin, and protein 4.1 provide another means whereby actin is linked to the plasma membrane in addition to the known adherens junctions in the lens. © 2004 Wiley‐Liss, Inc.
Induction of osteoblast differentiation indices by statins in MC3T3‐E1 cells
Authors: Maeda Toyonobu , Matsunuma Ayako , Kurahashi Izuru , Yanagawa Toru , Yoshida Hiroshi , Horiuchi Noboru 
Published: May 2004

AbstractStatins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc.