bluuebunny/crossref_metadata_2025_split huggingface dataset:
K‐ras mutation in tamoxifen‐related endometrial polyps
Authors: Hachisuga Toru , Miyakawa Takashi , Tsujioka Hiroshi , Horiuchi Shinji , Emoto Makoto , Kawarabayashi Tatsuhiko 
Published: October 2003

AbstractBACKGROUNDK‐ras mutation is thought to occur at an early stage of neoplastic progression in the endometrium. The authors investigated mutations in codon 12 of K‐ras in tamoxifen (TAM)‐related endometrial polyps.METHODSDNA was extracted from 11 frozen endometrial polyps from TAM‐treated patients with breast carcinoma. Mutations were detected using the mutant allele–specific amplification method. The results subsequently were analyzed for correlations with immunohistochemical data that were obtained using antibodies against estrogen receptors (ERs; α and β forms), progesterone receptors (PRs; A and B forms), and Ki‐67.RESULTSMutations in codon 12 of K‐ras were observed in 7 of 11 TAM‐related endometrial polyps. Expression levels of ER‐α and PR‐B were high in the glandular epithelium and low in the stroma. PR‐A expression was high in both the glandular epithelium and the stroma. In the glandular epithelium, expression of ER‐β appeared to be lower than expression of ER‐α. The Ki‐67 index in the glandular epithelium ranged from 2 to 38, whereas the index ranged from 0 to 4 in the stroma (P < 0.01).CONCLUSIONSThe incidence of mutations in codon 12 of K‐ras in TAM‐related endometrial polyps (64%) was greater than the incidence of these same mutations in sporadic endometrial hyperplasias (4.5–23%). High expression levels of ER‐α, PR‐A, and PR‐B in the glandular epithelium were observed in all polyps, regardless of K‐ras codon 12 mutation status and Ki‐67 index. The authors' findings may support the hypothesis that the polyp‐carcinoma sequence partly indicates the development of endometrial carcinoma in postmenopausal women who have been treated with TAM. Cancer 2003. © 2003 American Cancer Society.
Chromosomal abnormalities in Philadelphia chromosome‐negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome‐positive chronic myelogenous leukemia in chronic phase
Authors: Medina Jorge , Kantarjian Hagop , Talpaz Moshe , O'Brien Susan , Garcia‐Manero Guillermo , Giles Francis , Rios Mary Beth , Hayes Kimberly , Cortes Jorge 
Published: October 2003

AbstractBACKGROUNDAnecdotal cases of chromosomal abnormalities in Philadelphia chromosome (Ph)‐negative metaphases have been reported in patients with chronic myelogenous leukemia (CML) in the chronic phase during treatment with interferon and, more recently, with imatinib. This phenomenon is different from true clonal evolution in that the additional cytogenetic abnormality occurs in Ph‐negative cells.METHODSThe authors analyzed their experience with 342 patients with CML in chronic phase treated with imatinib to investigate the frequency and significance of this event.RESULTSAfter a median follow‐up of 30 months (range, 16–35 months), 21 patients (6%; 95% confidence interval, 0.04, 0.09) developed 25 chromosomal abnormalities in Ph‐negative cells. Thirteen (54%) of these abnormalities were seen in 2 or more metaphases. The median time from the start of treatment with imatinib to the appearance of the abnormalities was 6 months (range, 3–22 months). The most common cytogenetic abnormality detected was trisomy 8 (33%). Twenty of 21 patients (95%) achieved a major (Ph < 35%) cytogenetic response (complete cytogenetic response in 13–62%). After a median follow‐up of 22 months (range, 4–33 months), all 21 patients were alive, 20 of them in chronic phase and in complete hematologic response. None of the patients showed features of myelodysplasia.CONCLUSIONSCytogenetic abnormalities occur in Ph‐negative cells in a fraction of patients with CML in chronic phase treated with imatinib. With a short follow‐up, no clear clinical consequences can be identified. Cancer 2003. © 2003 American Cancer Society.
A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma
Authors: Han Ji‐Youn , Lee Dae Ho , Kim Hae Young , Hong Eun Kyung , Yoon Sung Min , Chun Jong Ho , Lee Hong Gi , Lee Sung Young , Shin Eun Hee , Lee Jin Soo 
Published: October 2003

AbstractBACKGROUNDDocetaxel is an active agent in advanced nonsmall‐cell lung carcinoma (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We conducted the current Phase II study to evaluate the efficacy and safety of the docetaxel/capecitabine combination in chemotherapy‐naive patients with advanced NSCLC.METHODSEligibility required Stage IIIB or IV NSCLC, bidimensionally measurable disease, and an Eastern Cooperative Oncology Group performance score of 2 or lower. Treatment consisted of docetaxel 36 mg/m2 intravenously on Days 1 and 8 plus capecitabine 1000 mg/m2 orally twice per day on Days 1–14 of a 21‐day cycle, for a maximum of 6 cycles.RESULTSOf 39 patients enrolled, 39 and 36 patients were evaluated for toxicity and response, respectively. The overall response rate was 53% (95% confidence interval [CI], 37–69%) with 19 partial responses (no complete response). The median duration of response was 6.2 months (range, 2.1–15.7 months). At a median follow‐up of 14.2 months, 19 patients died. The median overall survival time was 17.8 months, with a 1‐year survival rate of 56.4% (95% CI, 40.9–72.0%). There were two treatment‐related deaths (one death due to pneumonia and one due to sepsis). Hematologic toxicity was mild to moderate. Thirteen percent of the patients had Grade 3 or 4 neutropenia. However, Grade 2 or 3 nonhematologic toxicities were frequent, which included asthenia (51%), stomatitis (33%), hand–foot syndrome (33%), and diarrhea (29%).CONCLUSIONSThe docetaxel/capecitabine combination showed promising antitumor activity for chemotherapy‐naive patients with advanced NSCLC, However, it was frequently associated with moderate‐to‐severe nonhematologic toxicities, suggesting clinical synergism in both efficacy and toxicity. Further adjustment of the dose schedule is recommended to maximize the therapeutic index. Cancer 2003. © 2003 American Cancer Society.
Reduced folate carrier protein expression in osteosarcoma
Authors: Ifergan Ilan , Meller Issac , Issakov Josefin , Assaraf Yehuda G. 
Published: October 2003

AbstractBACKGROUNDHigh‐dose methotrexate (MTX) is an important component of current protocols for the treatment of osteosarcoma. Although MTX uptake proceeds primarily through the reduced folate carrier (RFC) protein and efflux occurs via multidrug resistance protein 1 (MRP1), RFC protein expression in osteosarcoma remains unexamined.METHODSRFC and MRP1 expression (normalized to β‐actin expression) was examined with Western blot analysis in 11 osteosarcoma specimens obtained at diagnosis and 9 osteosarcoma specimens obtained on recurrence.RESULTSThe average RFC level in specimens obtained on recurrence was significantly higher than the level in specimens obtained at diagnosis (P = 0.0005). Furthermore, in all three matched pairs of diagnosis and recurrence specimens, RFC levels were higher in recurrence specimens than in the corresponding diagnosis specimens. Potential correlations between RFC and MRP1 expression and histologic response to preoperative chemotherapy were examined. Tumors with poor histologic responses (i.e., ≤ 90% necrosis) had significantly lower RFC levels than did those with favorable responses to chemotherapy (P = 0.0016). In contrast, there was no correlation between MRP1 levels at diagnosis and histologic response to chemotherapy (P = 0.8764). The elevated MRP1 levels in specimens obtained on recurrence relative to MRP1 levels in specimens obtained at diagnosis were not statistically significant (P = 0.2056).CONCLUSIONSThe significant correlation between low RFC levels at diagnosis and poor histologic response to preoperative chemotherapy suggests that RFC levels at diagnosis may be a useful predictor of chemosensitivity and warrants large‐scale studies. In addition, postchemotherapy progression to recurrence is associated with a significant increase in RFC expression. To our knowledge, the current study is the first to examine RFC protein levels in tumor specimens. Cancer 2003. © 2003 American Cancer Society.
Familial sarcoma
Authors: Lynch Henry T. , Deters Carolyn A. , Hogg David , Lynch Jane F. , Kinarsky Yulia , Gatalica Zoran 
Published: October 2003

AbstractBACKGROUNDPartially due to the rare occurrence of soft tissue and osteogenic sarcomas in the general population, scant attention has been given to their hereditary etiology. Their overall poor prognosis might be ameliorated through an understanding of their environmental and hereditary causal factors, and/or their interactions, thereby contributing to earlier diagnosis and even the development of molecularly based targeted therapy.METHODSThe authors selected 10 sarcoma‐prone families from their extensive hereditary cancer‐prone family resource and focused on their challenging diagnostic, surveillance, and management features. The family study protocol included the compilation of a detailed family history of malignant disease of all anatomic sites and the collection of all available primary medical and pathology documents for verification. Genetic counseling was provided before DNA collection and at disclosure of results.RESULTSThese families displayed marked phenotypic and genotypic heterogeneity. In one of these families, 16 relatives had sarcomas, with 2 of the 16 each having 2 metachronous sarcomas; to our knowledge, this represents the greatest number of sarcomas reported in any family described to date. Two familial atypical multiple‐mole melanoma syndrome kindreds with the CDKN2A mutation showed the association of sarcoma with malignant melanoma, whereas one family had several pancreatic carcinomas. Other families with sarcoma had hereditary nonpolyposis colorectal carcinoma with MSH2 mutation, hereditary breast carcinoma with BRCA1 mutation, and p53 mutation in a Li–Fraumeni syndrome.CONCLUSIONSSarcoma‐prone families reported in the current study were selected carefully to depict clinicopathology and compliance features, the understanding of which could elucidate the etiologic role of genetic factors in concert with the phenotypic and genotypic heterogeneity encountered in such families. The lack of a population‐based data set for these families posed a limitation. Cancer 2003. © 2003 American Cancer Society.
cPLA2 activator peptide, PLAP, increases arachidonic acid release and apoptosis of vascular smooth muscle cells
Authors: Pilane Cyril M. , LaBelle Edward F. 
Published: October 2003

AbstractApoptosis of vascular smooth muscle cells (VSMCs) has recently drawn a lot of interest in various laboratories due to its importance in atherogenesis. We have shown previously that nitric‐oxide (NO) can induce apoptosis of VSMCs and that the NO‐induced apoptosis is accompanied by an increase in arachidonic acid release via cytoplasmic Ca2+‐dependent phospholipase A2 (cPLA2). We have demonstrated here that NO‐induced activation of cPLA2 leading to increased arachidonic acid release can be mimicked via direct activation of cPLA2 with a cPLA2 activator peptide, PLAP. The PLAP induced arachidonic acid release and apoptosis is inhibitable by a cPLA2‐specific inhibitor, AACOCF3, indicating the direct involvement of cPLA2. In this study, activation of cPLA2 appears to be preceded by activation and binding by PLAP indicating that the cPLA2 functions are mediated via PLAP. J. Cell. Physiol. 198: 48–52, 2004. © 2003 Wiley‐Liss, Inc.
Cationic polyelectrolyte hydrogel fosters fibroblast spreading, proliferation, and extracellular matrix production: Implications for tissue engineering
Authors: De Rosa Mario , Carteni' Maria , Petillo Orsolina , Calarco Anna , Margarucci Sabrina , Rosso Francesco , De Rosa Alfredo , Farina Ernesto , Grippo Pasquale , Peluso Gianfranco 
Published: October 2003

AbstractFibrous encapsulation is known to occur to many prosthetic implants and is thought to be due to the cells not adhering adequately to the surface. For developing new materials able to enhance cellular adhesion by mimicking extracellular matrix components, polyelectrolyte polymers, characterized by tunable surface charges, have been proposed. Here we demonstrate that panoply of cell functions over a two‐dimensional substratum is influenced by surface charge. We have at first generated structurally related polyelectrolyte substrata varying in their positive surface charge amount and subsequently evaluated a variety of behaviors of human primary fibroblasts seeded on these polymers. The proportion of adherent, spreading, and proliferating cells was increased significantly on cationic hydrophilic surfaces when compared with the neutral base surface. The extent of cell spreading correlated with cytoskeleton organization as assessed using immunofluorescence techniques. In the key experiment, the presence of cationic charges on cell adhesion‐resistant neutral surface increased the synthesis of collagen I and III, the release of their metabolites, and the expression of their mRNA by fibroblasts. Interestingly, the scarce collagen deposits on neutral polymer consisted, for the most part, of collagen I while collagen III was present only in traces probably due to the secretion of metalloproteinase‐2 by non‐adherent fibroblasts. Taken together, these results show that polyelectrolyte films may promote the attachment of fibroblast cells as well as their normal secretory phenotype. Both effects could be potentially useful in integrating soft connective tissue to the implant, decreasing the chance of its fibrous encapsulation. J. Cell. Physiol. 198: 133–143, 2004. © 2003 Wiley‐Liss, Inc.
Gingival and dermal fibroblasts produce interleukin‐1β converting enzyme and interleukin‐1β but not interleukin‐18 even after stimulation with lipopolysaccharide
Authors: Tardif François , Ross Geneviève , Rouabhia Mahmoud 
Published: October 2003

AbstractEpithelial cells play a critical role in periodontal disease through the secretion of pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β) and interleukin‐18 (IL‐18). However, the role played by fibroblasts is still unclear. The rationale of this study was to throw light on the role of gingival fibroblasts in periodontal disease. We thus investigated the expression of IL‐1β, IL‐18, and ICE mRNA and the secretion of the corresponding proteins by human normal gingival fibroblasts before and after stimulation with lipopolysaccharide (LPS) from Porphyromonas gingivalis and Escherichia coli. IL‐1β, IL‐18, and ICE mRNA expression was evaluated by RT‐PCR. Proteins were analyzed by Western blot and ELISA. We demonstrated that gingival fibroblasts expressed ICE mRNA. Basal expression of ICE was modulated following cell stimulation with lipopolysaccharide (5 μg/ml). However, gingival fibroblasts expressed low levels of IL‐1β mRNA. The expression was potentiated by LPS. The expression of IL‐1β mRNA was followed by the secretion of IL‐1β but not IL‐18 protein. Our study suggests that fibroblasts may be involved in the defense against infections via an IL‐1β‐mediated but not an IL‐18‐mediated mechanism. J. Cell. Physiol. 198: 125–132, 2004. © 2003 Wiley‐Liss, Inc.
Teaching biotechnology through case studies—can we improve higher order thinking skills of nonscience majors?
Authors: Dori Yehudit J. , Tal Revital T. , Tsaushu Masha 
Published: October 2003

AbstractTeaching nonscience majors topics in biotechnology through case studies is the focus of this research. OurBiotechnology, Environment, and Related Issuesmodule, developed within theScience for Allframework, is aimed at elevating the level of students' scientific and technological literacy and their higher order thinking skills. The research goal was to investigate nonscience major students' ability to use various thinking skills in analyzing environmental and moral conflicts presented through case studies in the Biotechnology Module. The research population consisted of about 200 nonscience majors in eight classes of grades 10–12 from heterogeneous communities. We found a significant improvement in students' knowledge and understanding and higher order thinking skills at all academic levels. The scores that low academic level students achieved in the knowledge and understanding category were higher than their high academic level peers' scores. In the higher order thinking skills—question posing, argumentation, and system thinking—a significant difference in favor of the high academic level students was found. The gap that had existed between low and high academic level students narrowed. Most students reported that the biotechnological topics that they had studied were interesting and relevant. Based on these results, we advocate a curriculum that exposes students to scientific controversies through case studies with environmental and moral implications. Our research has shown that this approach is likely to contribute to developing scientific and technological literacy along with higher order thinking skills of nonscience majors. © 2003 Wiley Periodicals, Inc.Sci Ed87:767–793, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10081
Science teachers' diagnosis and understanding of students' preconceptions
Authors: Morrison Judith A. , Lederman Norman G. 
Published: October 2003

AbstractResearch has established that students enter their science classes with ideas about the natural world that do not align with accepted scientificbeliefs. The diagnosis of these student preconceptions may be seen as aninitial, crucial step in the process of teacher‐facilitated conceptualchange. So as to capture what science teachers do in their everydayclassroom routines to diagnose these student preconceptions, in‐depthobservations and interviews were conducted with four exemplary secondaryscience teachers. The teachers' strategies for diagnosing students' preconceptions, their use of information found through diagnosis, and the teachers' understanding of students' preinstructional ideas were all analyzed. The four teachers in this study did not use any formal assessment tools such as pretests, concept maps, interviews, or journal writing to diagnose students' ideas, although they all stated that finding out what students know prior to instruction is important. The teachers all declared that they used questioning to gather information on student ideas but were seen in their classes to rely heavily on low‐level, recall questions. One of the teachers, the most experienced, did conduct class discussions where the students were encouraged to express their ideas and preconceptions. The four teachers' understanding of what student preconceptions consist of and the justification for attempting to diagnose these ideas was seen to be weak.The implications of these findings and recommendations for teacher trainingare made in the article. © 2003 Wiley Periodicals, Inc. Sci Ed 87:849–867, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10092
Population structure of coypus (Myocastor coypus) in their region of origin and comparison with introduced populations
Authors: Guichón M. Laura , Doncaster C. Patrick , Cassini Marcelo H. 
Published: October 2003

AbstractThe first population recapture study of indigenous coypus Myocastor coypus is reported in protected areas of Argentine pampas within a region where the species is hunted for food and fur. Quarterly live trapping at two sites captured a high proportion of all coypus present (96% of juveniles; 85% of adults, independently of season, site and sex). Survival (from mortality or emigration) was constant across sites and seasons, and higher for juvenile males than females (88% and 71%, respectively) and lower for adult males than females (45% and 81%). Most turn‐over in numbers was replaced by births, and immigrating males tended to be the largest individuals present. Sex ratios were male‐biased amongst juveniles and female‐biased amongst adults. Taken together, these results are consistent with local resource competition in habitat rendered low in quality by crowding inside the locally protected areas. The indigenous coypu population matured more slowly, and to a smaller maximum body size, than coypus studied in introduced populations in North America and particularly in northern Europe. Cold European winters may have contributed to the evolution of precocious sexual maturity and larger body sizes in European compared with indigenous populations.
Activity patterns, home ranges and burrow use of aardvarks (Orycteropus afer) in the Karoo
Authors: Taylor W. A. , Skinner J. D. 
Published: October 2003

AbstractEight aardvarks Orycteropus afer were fitted with radio‐transmitters at Tussen die Riviere Nature Reserve between June 1996 and December 1997. Two became habituated and could be approached to a distance of 1 m. Activity patterns, home ranges and burrow use were investigated using telemetry and direct observations. In winter, aardvarks emerged above ground earlier, returned to burrows earlier and were active for shorter periods than in summer. They were nocturnal except occasionally in winter when some individuals foraged above ground before sunset. Home ranges varied between 133 ha and 302 ha and range overlap occurred within and between both sexes. Densities were c. eight animals per 1000 ha. Aardvarks used steep slopes (>15°) less than would have been expected according to availability. Average lengths of consecutive burrow use for three aardvarks were 4.9, 6.9 and 8.6 days, with some burrows being abandoned after only 1 day and one burrow being used for 38 days.
Are children of Holocaust survivors less well‐adapted? A meta‐analytic investigation of secondary traumatization
Authors: van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J. , Sagi‐Schwartz Abraham 
Published: October 2003

AbstractH. Keilson (1979) coined the term “sequential traumatization” for the accumulation of traumatic stresses confronting the Holocaust survivors before, during, and after the war. A central question is whether survivors were able to raise their children without transmitting the traumas of their past. Through a series of meta‐analyses on 32 samples involving 4,418 participatns, we tested the hypothesis of secondary traumatization in Holocaust survivor families. In the set of adequately designed nonclinical studies, no evidence for the influence of the parents' traumatic Holocaust experiences on their children was found. Secondary traumatization emerged only in studies on clinical participants, who were stressed for other reasons. A stress‐diathesis model is used to interpret the absence of secondary traumatization in nonclinical offspring of Holocaust survivors.
Co‐twin control study of relationships among combat exposure, combat‐related PTSD, and other mental disorders
Authors: Koenen Karestan C. , Lyons Michael J. , Goldberg Jack , Simpson John , Williams Wesley M. , Toomey Rosemary , Eisen Seth A. , True William , Tsuang Ming T. 
Published: October 2003

AbstractThe well‐documented association between combat‐related PTSD (C‐PTSD) and other mental disorders may be an artifact of shared familial vulnerability. This study uses a co‐twin control design to examine whether the association between C‐PTSD and other mental disorders persists after adjusting for shared familial vulnerability. Data were from male monozygotic‐twin pairs in the Vietnam Era Twin Registry. Logistic regression analyses demonstrated that combat exposure, adjusted for C‐PTSD, was significantly associated with increased risk for alcohol and cannabis dependence and that C‐PTSD mediated the association between combat exposure and both major depression and tobacco dependence. We conclude C‐PTSD comorbidity persists after controlling for shared vulnerability. Combat exposure is directly and indirectly, through C‐PTSD, associated with increased risk for other mental disorders.