bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies
Authors: Fracasso Paula M. , Rodriguez Luis C. , Herzog Thomas J. , Fears Carole L. , Goodner Sherry A. , Govindan Ramaswamy , Picus Joel , Rader Janet S. , Tan Benjamin R. , Arquette Matthew A. 
Published: July 2003

AbstractBACKGROUNDPegylated liposomal doxorubicin (PEG‐LD) and docetaxel have single‐agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies.METHODSTwenty‐two patients were enrolled in this two‐arm, accelerated, dose escalation trial. Both drugs were administered on Days 1 and 15 of a 28 day cycle. In Arm A, dose escalation proceeded from a sequence and starting dose of 15 mg/m2 PEG‐LD and 30 mg/m2 docetaxel. In Arm B, dose escalation proceeded from a sequence and starting dose of 30 mg/m2 docetaxel and 15 mg/m2PEG‐LD. In both arms, the dose of each drug was increased alternately by 5 mg/m2 at each dose level.RESULTSThe MTD for Arm A was 20 mg/m2 PEG‐LD and 40 mg/m2 docetaxel, both of which were administered on Days 1 and 15 of a 28‐day cycle. The MTD for Arm B was 35 mg/m2 docetaxel and 20 mg/m2 PEG‐LD, both of which were administered on Days 1 and 15 of a 28‐day cycle. Dose‐limiting toxicities were Grade 3 (according to the National Cancer Institute Common Toxicity Criteria) skin toxicity and thrombocytopenia. One partial response was observed and stable disease was documented for three patients.CONCLUSIONSThe recommended sequence and dose is 20 mg/m2 PEG‐LD followed by 40 mg/m2 docetaxel on Days 1 and 15 of a 28‐day cycle in Phase II trials for patients with breast and ovarian carcinoma to establish the efficacy of this well tolerated regimen. Cancer 2003;98:610–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11547
Rhabdomyosarcoma in adults
Authors: Ferrari Andrea , Dileo Palma , Casanova Michela , Bertulli Rossella , Meazza Cristina , Gandola Lorenza , Navarria Pierina , Collini Paola , Gronchi Alessandro , Olmi Patrizia , Fossati‐Bellani Franca , Casali Paolo G. 
Published: July 2003

AbstractBACKGROUNDThe goal of the current study was to clarify treatment outcomes for adult patients with rhabdomyosarcoma (RMS). Published series have reported definitively worse results for adults with RMS compared with children with RMS. This finding casts doubt on whether RMS is the same disease in adults as it is in children.METHODSOf 190 patients with RMS who were age 18 years or older and whose cases were recorded over a 25‐year span in the pathology database of the Istituto Nazionale Tumori (Milan, Italy), 171 could be analyzed retrospectively for treatment outcome. The authors attempted to stratify patients according to the degree to which they had been treated appropriately, based on current treatment guidelines for childhood RMS.RESULTSThe overall rate of response to chemotherapy was 85%. For the entire series, 5‐year event‐free survival and 5‐year overall survival (OS) were 28% and 40%, respectively. Among the 110 patients with embryonal, alveolar, or ‘not otherwise specified’ RMS, 5‐year OS was 46%; however, 5‐year OS was 61% for patients within this group (39% of the total) who had high scores for appropriate treatment.CONCLUSIONSThe current series parallels other published series in that it confirms the finding of a relatively poor long‐term outcome for adult patients with RMS. However, for patients whose treatment adhered to the current guidelines for treatment of children, outcome was similar to what has been reported in pediatric series. In addition, the rate of response to chemotherapy for the entire series was similar to the rate typically observed among children. These findings suggest that adults and children with RMS should receive similar treatment. Treatment protocols adopted from pediatric programs but tailored to adults could increase adults' chances of receiving appropriate treatment; prospective studies are needed to test this idea. Cancer 2003;98:571–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11550
Levels of the soluble, 55‐kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence
Authors: Wu Shuling , Korte Alexander , Gessner Reinhard , Henze Guenter , Seeger Karlheinz 
Published: July 2003

AbstractBACKGROUNDIt has been shown that the soluble, 55‐kilodalton isoform of tumor necrosis factor receptor (sTNFRp55) enhances tumor survival by exhibiting competitive ligand binding. The objective of the current study was to determine the levels of sTNFRp55 and their impact on outcome in 106 children with acute lymphoblastic leukemia (ALL) in first recurrence.METHODSBetween January 1997 and December 2001, bone marrow (BM) samples were collected from 106 children with a first recurrence of ALL at diagnosis. These patients were enrolled in the Berlin–Frankfurt–Münster (BFM) ALL recurrence trial, ALL‐REZ BFM 90‐96. Levels of sTNFRp55 in BM samples were determined with a commercially available enzyme‐linked immunosorbent assay kit. Event‐free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate.RESULTSThe mean sTNFRp55 level (± standard deviation) was 3.40 ± 2.57 ng/mL. High levels of sTNFRp55 were associated with shorter duration of first complete remission and observation time as well as poor response to chemotherapy. Most importantly, the probability of EFS (pEFS) at 3 years was significantly worse for children with recurrent ALL who had sTNFRp55 levels greater than the median value (> 2.77 ng/mL) compared with patients who had levels that were less than the median value (pEFS: 0.44 ± 0.10 ng/mL vs. 0.12 ± 0.10 ng/mL; P = 0.006). It is noteworthy that the sTNFRp55 levels in 22 children with recurrent, TEL‐AML1‐positive ALL ([t(12;21)(p13;q22)]; 2.69 ± 1.05 ng/mL) were significantly lower compared with the levels in children who had TEL‐AML1‐negative ALL (3.34 ± 1.49 ng/mL; P < 0.05).CONCLUSIONSThe results indicated that a high sTNFRp55 level represents a negative prognostic factor for children with recurrent ALL in terms of EFS and overall survival. Cancer 2003;98:625–31. © 2003 American Cancer Society.DOI 10.1002/cncr.11553
Multiple primary tumors involving cancer of the brain and central nervous system as the first or subsequent cancer
Authors: Inskip Peter D. 
Published: July 2003

AbstractBACKGROUNDThis study was undertaken to determine whether cancer of the brain and central nervous system (CNS) occurs together with other types of cancer more often or less often than would be expected due to chance.METHODSThe study was based on data collected by the Surveillance, Epidemiology, and End Results (SEER) Program for cancers diagnosed in the U.S. between 1973 and 1998. The standardized incidence ratio (SIR) for new malignancies was estimated as the number of patients diagnosed with a particular type of cancer (observed), divided by the number of diagnoses expected based on person‐years of follow‐up and incidence rates for SEER cancer registries.RESULTSAmong patients who were diagnosed first with cancer of the brain or CNS, statistically significant excesses were observed for cancers of bone (SIR = 14.4), soft tissue (SIR = 4.6), brain and CNS (SIR = 5.9), salivary gland (SIR = 5.1), and thyroid gland (SIR = 2.7) in addition to acute myelocytic leukemia (SIR = 4.1) and melanoma of the skin (SIR = 1.7). Excess risk of new malignancies was markedly greater after first cancers of the brain or CNS diagnosed in childhood compared with similar diagnoses in adulthood. In reverse associations, significant excesses of cancer of the brain and CNS were observed only after diagnoses of acute lymphocytic leukemia (SIR = 7.4) and cancer of the testis (SIR = 1.8) or the thyroid gland (SIR = 1.7).CONCLUSIONSCancer treatment appears to have been the major factor underlying most of the positive associations between brain cancer and primary cancers of other types, with a probable lesser contribution from shared genetic susceptibility. Results provide little or no evidence that brain cancer shares important etiologic factors with the common cancers of adulthood. Cancer 2003;98:562–70. Published 2003 by the American Cancer Society.DOI 10.1002/cncr.11554
Oxidative stress is generated via the mitochondrial respiratory chain during plant cell apoptosis
Authors: Weir Iona E. , Pham Nhu‐An , Hedley David W. 
Published: July 2003

AbstractBackgroundWe present evidence that in plant cells DNA damage induced by the topoisomerase trapping drug camptothecin induces oxidative stress via the mitochondrial respiratory chain.MethodsFlow cytometry was used to analyse mitochondrial respiratory chain activity by simultaneous measurement of mitochondrial generation of reactive oxygen intermediates (ROI) and mitochondrial membrane potential (ΔΨm), in live functioning sugarbeet protoplasts. The mitochondrial respiratory chain function was assessed by the addition of substrate and inhibitors to the digitonin‐permeabilised protoplasts. Mitochondrial activity was also measured in protoplasts at different stages of induced apoptosis by camptothecin.ResultsThe addition of camptothecin to sugarbeet protoplasts resulted in increased mitochondrial generation of ROI, occurring concurrently with the hyperpolarisation of the mitochondrial inner membrane. Subsequently, there was a decrease in mitochondrial‐generated ROI, in association with a decrease in ΔΨm. These camptothecin‐treated digitonin‐permeabilised protoplasts could be re‐energised and ROI decreased by the addition of malic acid in the early stages of apoptosis induction, but not in the latter stages. There was a depolarisation of the mitochondrial inner membrane in the final stages of apoptosis.ConclusionsThese results are consistent with impaired adenine nucleotide exchange across the mitochondrial membrane, suggesting that similar mechanisms regulate plant apoptosis as those described for mammalian apoptosis. Cytometry Part A 54A:109–117, 2003. © 2003 Wiley‐Liss, Inc.
NF‐κB inhibitor sesquiterpene parthenolide induces concurrently atypical apoptosis and cell necrosis: Difficulties in identification of dead cells in such cultures
Authors: Pozarowski Piotr , Halicka Dorota H. , Darzynkiewicz Zbigniew 
Published: July 2003

AbstractBackgroundApoptosis and necrosis (“accidental cell death”) are distinct modes of cell death. The feature that often distinguishes apoptotic from necrotic cells is preservation of the plasma membrane integrity, reflected by ability of the former cells to exclude cationic dyes such as propidium iodide (PI) for a certain length of time. During necrosis, the plasma membrane is rapidly ruptured and necrotic cells stain intensely with PI. While studying cytostatic effects of the anti‐inflammatory sesquiterpene parthenolide (PRT), we have noticed that, concurrent with apoptosis, the cells were dying by necrosis in the same cultures. Furthermore, because apoptosis was atypical, reflected by rapid loss of plasma membrane integrity, it was difficult to distinguish apoptotic from necrotic cells based on this feature.MethodsThree methods were used to distinguish apoptosis from necrosis: (a) HL‐60 cells treated with PRT were subjected to analysis of caspases activation using antibody that detects activated (cleaved) caspase‐3, (b) apoptotic cells were identified by binding of fluorochrome‐labeled inhibitor of caspases FAM‐VAD‐FMK combined with the PI exclusion assay, and (c) cellular DNA and RNA were differentially stained with acridine orange (AO).ResultsApoptotic cells were characterized by (a) caspase‐3 activation detected immunocytochemically and (b) binding of FAM‐VAD‐FMK followed by or concurrent with (c) loss of ability to exclude PI, (d) deficit in DNA content, and (e) relatively little changed RNA content. Necrotic cells showed (a) no evidence of caspase‐3 activation, (b) no binding of FAM‐VAD‐FMK, (c) inability to exclude PI, (d) rapid loss of RNA, and (e) unchanged DNA content.ConclusionsIdentification of apoptotic cells versus necrotic cells was possible either based on the evidence of caspase‐3 activation, by labeling with FAM‐VAD‐FMK combined with PI or by differential staining of cellular DNA and RNA with AO. The data indicate that plasma membrane appears to be one of the targets of PRT, because its integrity is lost very early during cell death, which is reflected by atypical apoptosis and by primary necrosis (lysis of the membrane). Cytometry Part A 54A:118–124, 2003. © 2003 Wiley‐Liss, Inc.
Novel method for the isolation and characterisation of the putative prostatic stem cell
Authors: Bhatt Rupesh I. , Brown Michael D. , Hart Claire A. , Gilmore Paul , Ramani Vijay A.C. , George Nicholas J. , Clarke Noel W. 
Published: July 2003

AbstractBackgroundProstate stem cells, responsible for the development, maturation, and function of the prostate, have been implicated in the aetiology of both benign prostate hyperplasia (BPH) and prostate cancer (CaP). However, research has been hampered by the lack of a definitive stem cell marker. We have adapted the protocol for differential Hoechst 33342 uptake by hemopoietic stem cells to enable isolation of putative stem cells from the prostate.MethodsProstate epithelial cells isolated from prostate tissue obtained from patients with BPH after transurethral resection of the prostate were stained with Hoechst 33342. The Hoechst 33342 Red/Blue flow cytometry profile was then determined. Hoechst 33342 and Pyronin Y staining was used to determined the cell cycle status.ResultsA verapamil‐sensitive side population (SP) can be isolated from primary prostate tissue accounting for 1.38% ± 0.07% of prostate epithelial cells. Cell cycle analysis of this SP population revealed that the majority of SP cells are in either G0 (12.38 ± 0.31%) or G1 (63.19 ± 2.13%).ConclusionsThe Hoechst 33342 dye efflux protocol can be adapted for the isolation of a SP from primary prostate tissue. Cytometry Part A 54A:89–99, 2003. © 2003 Wiley‐Liss, Inc.
Sensitive and reliable JC‐1 and TOTO‐3 double staining to assess mitochondrial transmembrane potential and plasma membrane integrity: Interest for cell death investigations
Authors: Zuliani Thomas , Duval Raphaël , Jayat Chantal , Schnébert Sylviane , André Patrice , Dumas Marc , Ratinaud Marie‐Hélène 
Published: July 2003

AbstractBackgroundApoptosis is currently studied by flow cytometry with mitochondrial membrane potential (Δψmt) and membrane integrity fluorochromes. Rhodamine 123 and DiOC6(3) remain controversial to identify cells displaying a low Δψmt. JC‐1 constitutes a good Δψmt indicator, due to a fluorescence shift from green to orange emission, according to the increase in Δψmt. Nevertheless, it is not feasible to analyze it simultaneously with propidium iodide. Among available fluorescent probes, TOTO‐3 seems to be a good candidate for double staining with JC‐1.MethodsCell death of HaCaT cells was induced by H2O2 and FasL. Samples were stained with DiOC6(3)/IP or JC‐1/TOTO‐3 then analyzed by flow cytometry. Results were supported by confocal microscopy analyses of mitochondrial membrane potential. Moreover, cell morphology was determined on the sorted subpopulations defined on the basis of staining (JC‐1 versus TOTO‐3).ResultsWe found that JC‐1 is a more efficient mitochondrial probe than DiOC6(3). After stress induction, the fluorescence level of JC‐1 and TOTO‐3 clearly defined three fluorescent subpopulations, respectively: (1) JC‐1high and TOTO‐3low, (2) JC‐1low and TOTO‐3medium, and (3) JC‐1low and TOTO‐3high. Their morphologic aspects after cell sorting indicated that they corresponded to three functional states (intact, apoptotic, and necrotic cells), and data were supported by caspase activity measurements.ConclusionsWe propose a reliable and efficient staining, with JC‐1 and TOTO‐3 to discriminate three functional cellular states: intact, apoptotic, and necrotic/late apoptotic cells by flow cytometry. Cytometry Part A 54A:100–108, 2003. © 2003 Wiley‐Liss, Inc.
An aperture‐shifting light‐microscopic method for rapidly quantifying positions of cells in 3D matrices
Authors: Burton Kevin 
Published: July 2003

AbstractBackgroundRapid measurements of large numbers of cells in 3D are often required for measurements of cell migration. A method is presented for quantifying the position of cells in three‐dimensional gels using brightfield microscopy.MethodsImages were recorded using transmitted light with a closed condenser aperture diaphragm positioned off axis to produce oblique illumination. Two or more images, each at the same focal plane, were obtained with the aperture shifted equally to either side of the optical axis. All in‐focus objects were at the same position in the two images, but out‐of‐focus objects were displaced parallel to the aperture movement.ResultsThe method was tested using gels containing 12‐μm‐diameter glass beads or cells that had migrated several hundred micrometers into the gel. The position in the image plane varied linearly with axial position, being reversed for objects above and below the focal plane. Beads and cells could be visualized up to a depth of >1 mm in gels.ConclusionsThe method facilitates measurements of positions of cells in 3D matrices by eliminating the need to perform optical sectioning and can be used with any brightfield microscope.
Cytometry Part A 54A:125–131, 2003. © 2003 Wiley‐Liss, Inc.
Immunoreactivity of Stat5 phosphorylated on tyrosine as a cell‐based measure of Bcr/Abl kinase activity
Authors: Jacobberger James W. , Sramkoski R. Michael , Frisa Phyllis S. , Ye Peggy Peng , Gottlieb Megan A. , Hedley David W. , Shankey T. Vincent , Smith Bradley L. , Paniagua Mary , Goolsby Charles L. 
Published: July 2003

AbstractBackgroundStat51 (Signal Transducer and Activator of Transcription 5) is normally phosphorylated and activated by Janus kinases. In cells transformed with BCR/ABL, Stat5 is constitutively activated by promiscuous phosphorylation. Cytometry of intracellular antigens can be used to evaluate cell treatments affecting gene expression, because it precisely provides the fraction of affected cells and the quantitative change in expression. Here, we asked whether we could measure a phosphorylated epitope on Stat5 by cytometry, and whether that measurement would respond to Bcr/Abl inhibition.MethodsChronic myelogenous leukemia (CML) cell lines or control Bcr/Abl‐negative cells were treated or not with imatinib mesylate, fixed and permeabilized with formaldehyde followed by methanol; reacted with rabbit polyclonal and mouse monoclonal antibodies against an epitope including tyrosine 694 of Stat5a (pSTAT5); reacted with antibodies that mark mitotic cells; counterstained with secondary fluorescent antibodies and 4′,6‐diamidino‐2‐phenylindole (DAPI); and then subjected to flow cytometry. Western blotting was performed with pSTAT5 and Stat5 antibodies.ResultsOptimal fixation and staining parameters were established for pSTAT5 antibodies with K562 cells. These cells displayed high levels of immunoreactivity with pSTAT5 probes that could be inhibited uniformly with imatinib mesylate in a dose‐response and time‐dependent manner. The IC50 for downregulation of pSTAT5 immunoreactivity for K562 cells by cytometry was ∼70 nM. The inhibition half‐time was approximately 1 min. At micromolar doses this reactivity remained minimal for up to 7 days. Cultured cells also displayed a population of negative cells that increased under conditions related to cessation of cell growth (media nutrient depletion). This study also showed quantitatively that a rabbit polyclonal antibody that cross‐reacted with an additional epitope could be used successfully as a measure of Bcr/Abl activity.ConclusionWe have developed a sensitive cytometric assay for Bcr/Abl kinase activity in human hematopoietic cell lines. Cytometry Part A 54A:75–88, 2003. © 2003 Wiley‐Liss, Inc.
Nerve collagens from diabetic and nondiabetic Sprague–Dawley and biobreeding rats: an atomic force microscopy study
Authors: Wang H. , Layton B. E. , Sastry A. M. 
Published: July 2003

AbstractBackgroundAlterations in rat's nerve collagens due to diabetes may be related to the permanence of damage due to diabetic neuropathy. We (1) provide a methodology for determining the diameters of collagen fibers accounting for atomic force microscope (AFM) imaging artifacts, (2) present data on structural differences in sciatic nerve endoneurial, epineurial and tail tendon collagens of control and diabetic Sprague–Dawley and BioBreeding rats, and (3) compare results with literature values.MethodsWe measured collagen diameters and band spacing on endoneurial and epineurial sciatic nerve tissue, and tail tendon, in control and diabetic rats (STZ‐induced 12‐week diabetic SD and 16‐week spontaneously diabetic BB rats). We also developed a model to interpret the raw AFM data.ResultsAll types of fibrillar collagen diameters studied became larger for diabetic versus control animals. Values for diabetic and control collagen fiber diameters in SD rats were 78 nm and 72 nm for SN epineurium, and 49 nm and 43 nm for SN endoneurium. For diabetic and control BB rats, these values were 83 nm and 77 nm (SN epineurium) and 49 nm and 43 nm (SN endoneurium). Values of 161 nm and 125 nm were found for diabetic and control tail tendon of BB rats. No significant changes were observed in any of the five comparisons made in D‐band spacings that ranged from 63 to 69 nm.ConclusionsThe best means we have found to reduce raw AFM data is to measure several diameters with a single scan, using valley‐to‐valley measurements. Structural, fibrillar collagens of the nerve and tendon become larger in rats exposed to prolonged diabetes. Copyright © 2003 John Wiley & Sons, Ltd.