bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient tumor targeting by single‐domain antibody fragments of camels
Authors: Cortez‐Retamozo Virna , Lauwereys Marc , Hassanzadeh Gh. Gholamreza , Gobert Martine , Conrath Katja , Muyldermans Serge , De Baetselier Patrick , Revets Hilde 
Published: August 2002

AbstractThe variable domain of functional heavy chain antibodies (VHH) devoid of light chains, found in camels, constitute the smallest intact antigen‐binding domain fragment. Two camel single‐domain fragments, cAb‐Lys2 and cAb‐Lys3, recognizing an overlapping epitope of lysozyme with a dissociation constant of 2 nM and 65 nM, respectively, and a bivalent cAb‐Lys3 were investigated for their ability to target transgenic tumors expressing lysozyme on their membrane. Biodistribution studies revealed that these non‐immunogenic monomeric and bivalent camel single‐domain antigen binders specifically target lysozyme‐expressing tumors and metastatic lesions. The excess of antibody is rapidly eliminated from the blood circulation and no cAb retention was observed in normal organs. The tumor to organ cAb‐ratios at 2 and 8 hr were in the (2.1–10.8):1 and (6.2–23.7):1 range, respectively. The degree and specificity of tumor retention is independent of the affinity of the recombinant camel single‐domain fragments for their antigen and from their univalent monomeric (15 kDa) or bivalent format (33 kDa). This study demonstrates the successful and specific in vivo targeting of tumors by camel single‐domain fragments. It may open perspectives for their future use as tumor‐targeting vehicle, due to their small size, soluble behaviour and because they are non‐immunogenic and interact with epitopes that are less antigenic for conventional antibodies. © 2002 Wiley‐Liss, Inc.
Histologic classification of thymic epithelial tumors: Comparison of established classification schemes
Authors: Rieker Ralf J. , Hoegel Josef , Morresi‐Hauf Alicia , Hofmann Walter J. , Blaeker Hendrik , Penzel Roland , Otto Herwart F. 
Published: August 2002

AbstractThe object of our multicenter retrospective study was to compare the new histologic World Health Organization (WHO) classification and the classical histologic Bernatz classification in terms of interobserver agreement and prognostic importance. The influence of coexisting diseases was also analyzed using the Charlson score. We evaluated 218 patients from 5 different hospitals who were treated between 1967 and 1998. The statistical methods of analysis included Kaplan‐Meier estimates of survival curves and the application of Cox proportional hazards models to identify sets of prognostic factors for survival. Interobserver agreement was assessed by kappa coefficients. For both WHO and Bernatz classifications, interobserver agreement was good (weighted kappa > 0.87). However, the subdiversification of the “bioactive” WHO subgroup (B1, B2, B3) resulted in an interobserver agreement of only 0.49 within this group. In multivariable models, both the WHO classification and the Bernatz classification including carcinomas showed similar prognostic capabilities. The B3 type in the WHO classification and the predominantly epithelial type in the Bernatz classification had an intermediate prognostic ranking in comparison with the carcinomas and with the other subgroups. For both classifications, further simplification and subclassification into 3 subgroups led to classes with good discriminative power in respect to survival. In addition, very good interobserver agreement was observed in the simplified classifications. Comorbidity, sex, age of the patient and lymphofollicular hyperplasia had no major influence on overall survival. Both classifications showed similar prognostic power. Interobserver agreement of the type B subgroups was only moderate. By simplification of the classifications, subgroups with distinct survival could be identified. © 2002 Wiley‐Liss, Inc.
C‐myc gene expression alone is sufficient to confer resistance to antiestrogen in human breast cancer cells
Authors: Venditti Marcello , Iwasiow Barbara , Orr F. William , Shiu Robert P.C. 
Published: August 2002

AbstractC‐myc is implicated in the initiation, progression and estrogen response of breast cancer. To further investigate the role of c‐myc in breast cancer, we have developed clonal MCF‐7 human breast cancer cell lines harboring a stably‐transfected human c‐myc gene, whose expression was stringently controlled by the bacterial reverse tetracycline transcription activator protein. The expression of the endogenous genomic c‐myc gene in MCF‐7 cells was abolished by the potent pure estrogen antagonist, ICI 182,780. Functional c‐Myc protein was identified by both Western immunoblotting and by its ability to transactivate a chimeric plasmid consisting of E‐box sequences upstream of the luciferase reporter gene. One MCF‐7 clone, 35im, was chosen for further characterization. C‐myc induction by doxycycline was rapid and dose dependent; c‐myc mRNA appeared as early as 30 min after doxycycline addition and stimulation of c‐myc expression required as little as 50 ng/ml doxycycline, with c‐myc mRNA levels reaching a plateau at 2.5 μg/ml doxycycline. ICI 182,780 or doxycycline (a tetracycline analog) treatment did not alter the mRNA levels of Max, the c‐myc binding partner. As in wildtype MCF‐7 cells, the growth of clone 35im was inhibited by 1 μM or less of ICI 182,780 and stimulated by 10 nM to 1 μM 17β‐estradiol. When maintained in a complete medium containing 5% normal fetal bovine serum (FBS) and ICI 182,780, doxycycline induced cell growth by 400% in an 8‐day assay. A similar level of growth was achieved with doxycycline treatment in cells that were arrested by the use of charcoal‐stripped FBS. Doxycycline had no effect on the growth of a control MCF‐7 clone (18c). Apoptosis, assessed by caspase‐dependent cleavage of poly(ADP‐ribose) polymerase, was unchanged in clone 35im cells after treatments with doxycycline or ICI 182,780. The present study demonstrates that c‐myc alone is sufficient to confer antiestrogen resistance in human breast cancer. Our novel c‐myc‐inducible MCF‐7 cell model offers a unique opportunity to study the diverse actions of the c‐myc proto‐oncogene in human breast cancer. © 2002 Wiley‐Liss, Inc.
Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiangiogenin monoclonal antibody
Authors: Olson Karen A. , Byers H. Randolph , Key Marc E. , Fett James W. 
Published: August 2002

AbstractA neutralizing monoclonal antibody (MAb) 26‐2F to human angiogenin, a potent inducer of neovascularization, has been shown previously to prevent or delay the appearance of angiogenin‐secreting human colon, fibrosarcoma and lung tumor cell xenografts implanted subcutaneously (s.c.) into athymic mice. In an analogous model system, we report here that the antibody also prevents the establishment of PC‐3 androgen‐independent human prostate cancer tumors in, on average, 40% of treated mice (p < 0.0001, survivor analysis). Intriguingly, combining MAb 26‐2F together with cisplatin and suramin, 2 therapeutic agents that together showed little antitumor activity in the aforementioned model, resulted in an even greater degree of protection (71% protected, p = 0.009 compared to antibody treatment alone). This protective effect persisted several weeks after cessation of treatment. Additionally, prophylactic systemic administration of MAb 26‐2F dramatically reduced by 50% the formation of spontaneous regional metastasis originating from primary growth in the prostate gland of PC‐3M cells, highly metastatic variants of PC‐3. Protection from metastasis was still significant when treatment with MAb 26‐2F was delayed until after the primary tumor was well established. The antibody is not directly cytotoxic to either cell type, both of which secrete angiogenin in vitro and when growing as tumors in vivo, but changes the pattern of vascularity in primary tumors growing orthotopically. These findings, together with the observation that angiogenin protein and mRNA are apparently overexpressed in cancerous vs. normal human prostate tissues, demonstrate that angiogenin antagonism represents a promising new approach for preventing progression and metastasis of clinical prostate cancer. © 2002 Wiley‐Liss, Inc.
Healing of experimental colonic anastomoses: Effects of combined preoperative high‐dose radiotherapy and intraperitoneal 5‐fluorouracil
Authors: El‐Malt Mohamed , Ceelen Wim , van den Broecke Caroline , Cuvelier Claude , Van Belle Simon , De Neve Wilfried , de Hemptinne Bernard , Pattyn Piet 
Published: August 2002

AbstractTo study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham‐irradiated (SR). During the last 5 days of the irradiation schedule, 5‐fluorouracil (5‐FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy‐high dose [CH]) or a low dose (10 mg/kg, chemotherapy‐low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side‐to‐side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high‐dose 5‐FU alone. 5‐FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high‐dose 5‐FU induces more histological alterations at the anastomotic site. © 2001 Wiley‐Liss, Inc.
Adenosine acts through an A3 receptor to prevent the induction of murine anti‐CD3‐activated killer T cells
Authors: Hoskin David W. , Butler Jared J. , Drapeau Dennis , Haeryfar S.M. Mansour , Blay Jonathan 
Published: August 2002

AbstractAdenosine, a purine nucleoside found at high levels in solid tumors, is able to suppress the recognition/adhesion and effector phases of killer lymphocyte‐mediated tumor cell destruction. Here, we demonstrate that adenosine, at concentrations that are typically present in the extracellular fluid of solid tumors, exerts a profound inhibitory effect on the induction of mouse cytotoxic T cells, without substantially affecting T‐cell viability. T‐cell proliferation in response to mitogenic anti‐CD3 antibody was impaired in the presence of 10 μM adenosine (plus coformycin to inhibit endogenous adenosine deaminase). Antigen‐specific T‐cell proliferation was similarly inhibited by adenosine. Anti‐CD3‐activated killer T (AK‐T) cells induced in the presence of adenosine exhibited reduced major histocompatibility complex‐unrestricted cytotoxicity against P815 mastocytoma cells in JAM and 51Cr‐release assays. Diminished tumoricidal activity correlated with reduced expression of mRNAs coding for granzyme B, perforin, Fas ligand and tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), as well as with diminished Nα‐CBZ‐L‐lysine thiobenzylester (BLT) esterase activity. Interleukin‐2 and interferon‐γ synthesis by AK‐T cells was also inhibited by adenosine. AK‐T cells express mRNA coding for A2A, A2B and A3 receptors, but little or no mRNA coding for A1 receptors. The inhibitory effect of adenosine on AK‐T cell proliferation was blocked by an A3 receptor antagonist (MRS1191) but not by an A2 receptor antagonist (3,7‐dimethyl‐1‐propargylxanthine [DMPX]). The A3 receptor agonists (N6‐2‐(4‐aminophenyl)ethyladenosine [APNEA] and N6‐benzyl‐5′‐N‐ethylcarboxamidoadenosine [N6‐benzyl‐NECA]) also inhibited AK‐T cell proliferation. Adenosine, therefore, acts through an A3 receptor to prevent AK‐T cell induction. Tumor‐associated adenosine may act through the same mechanism to impair the development of tumor‐reactive T cells in cancer patients. © 2002 Wiley‐Liss, Inc.
Tumor‐infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer
Authors: Shirakawa Kazuo , Shibuya Masabumi , Heike Yuji , Takashima Shigemitsu , Watanabe Ichiro , Konishi Fumio , Kasumi Fujio , Goldman Corey K. , Thomas Kenneth A. , Bett Andrew , Terada Masaaki , Wakasugi Hiro 
Published: August 2002

AbstractInflammatory breast cancer (IBC) is a specific type of breast tumor that generally has a poor prognosis, in spite of recent advances in treatment. In the present study, semiquantitative reverse transcriptase polymerase chain reaction examination of resected specimens showed that angiogenic factors, not lymphangiogenic factors, are overexpressed in IBC tumors, compared with non‐IBC tumors. Immunohistochemical analysis of the specimens revealed a significantly higher population of tumor‐infiltrating (TI) endothelial cells (ECs) or endothelial precursor cells (EPCs) in tumor‐associated stroma of IBC specimens than in non‐IBC specimens. In a previous study, we examined the phenotype of host cells in response to transplanted IBC cells, using an established human IBC xenograft model (WIBC‐9) (Shirakawa et al., Cancer Res 2001;61:445–51). The data obtained in that study are consistent with the findings of the present study. To explore the therapeutic potential of blocking vascular endothelial growth factor (VEGF) and angiopoietin (Ang) pathways in IBC, established vectors encoding soluble Flt‐1 (sFlt‐1) and soluble Tie2 (sTie2) were injected directly into WIBC‐9. Both vectors produced growth inhibition ratios of WIBC‐9 that were significantly higher than those of a non‐IBC xenograft (MC‐5). Also, both vectors suppressed WIBC‐9 lung metastases. The efficacy correlated with the number of TI ECs/EPCs, which was determined by fluorescence‐activated cell sorting. These ECs/EPCs incorporated acetylated lipoprotein and were integrated within a HUVEC monolayer in vitro culture on day 5. © 2002 Wiley‐Liss, Inc.
NS‐398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines
Authors: Cheng Jidong , Imanishi Hiroyasu , Amuro Yoshiki , Hada Toshikazu 
Published: August 2002

AbstractCyclooxygenase 2 (COX‐2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX‐2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth‐inhibitory mechanism of a selective COX‐2 inhibitor, NS‐398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX‐2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS‐398 inhibited the growth of all 4 cell lines in a time‐ and dose‐dependent manner and the inhibitory effects were independent of the level of COX‐2 protein expression. PCNA expression was downregulated by NS‐398 in a dose‐independent manner. NS‐398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX‐2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS‐398 in hepatocellular carcinoma cell lines. © 2002 Wiley‐Liss, Inc.
Predictive value of histologic tumor necrosis after radiation
Authors: Chen Yuhchyau , Taghian Alphonse G. , Rosenberg Andrew E. , O'Connell John , Okunieff Paul , Suit Herman D. 
Published: August 2002

AbstractPostsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS‐26, SCC‐21, and HGL‐21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One‐half of the tumor was divided into 1‐mm3 fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCDp (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. © 2001 Wiley‐Liss, Inc.
Involvement of αvβ 3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix
Authors: Carreiras Franck , Thiébot Bénédicte , Leroy‐Dudal Johanne , Maubant Sylvie , Breton Marie‐france , Darbeida Halima 
Published: August 2002

AbstractLike the majority of tumor cells, ovarian cancer cell growth is critically dependent on their neovascularization. Adhesion molecules and cellular events that lead to ovarian tumor cell interactions with endothelial extracellular matrix surrounding the vasculature are poorly identified. To understand the role of αvβ3 integrin and its ligand fibronectin in this process, we used in vitro coculture models with IGROV1 human ovarian adenocarcinoma cell line and human umbilical vein endothelial cells (HUVEC). Adhesion assays revealed a strong ability of IGROV1 cells to adhere to HUVEC‐ECM. αvβ3 is mainly implicated and seems to cooperate with α5β1 integrin in this event. Immunofluorescence staining revealed the presence of αvβ3 and α5β1 in IGROV1 cells adhering on HUVEC‐ECM at regions of cell sub‐stratum contacts. Furthermore, our data showed the absence of fibronectin staining in IGROV1 cells and the disruption of the HUVEC‐ECM fibrillar fibronectin network under IGROV1 cell influence. In situ experiments in ovarian neoplastic tissue corroborated the absence of fibronectin in the tumor and its strong detection in vasculature. These findings suggest the active participation of αvβ3 and α5β1 integrins and the reorganization of endothelial fibronectin during the adhesion of IGROV1 cells to HUVEC‐ECM whereas IGROV1 cells seem to be unable to synthesize fibronectin. Thus, fibronectin integrin receptors expressed by ovarian tumor cells and endothelial fibronectin may be of importance in ovarian carcinoma neovascularization and during tumor‐vasculature interactions. © 2002 Wiley‐Liss, Inc.
Family transitions in Latin America: first intercourse, first union and first birth
Authors: Heaton Tim B. , Forste Renata , Otterstrom Samuel M. 
Published: August 2002

AbstractThis paper examines the initiation of sexual activity, first marriage and first birth as key steps in family formation. These events mark the transition to adulthood and generally occur in the late teens and early twenties in most Latin American countries. Using data from Demographic and Health Surveys, we examine the timing of these events across birth cohorts, comparing urban and rural areas, countries, cultural regions and educational groups. The average life course for young women in Latin America consists of the initiation of intercourse as adolescents, entering partnerships about one year later, and giving birth about a year after that. This pattern remained fairly stable over the time period examined. Education substantially delays these family transitions and the education effect is similar in most countries. Latin American women with secondary levels of schooling are significantly less likely to experience early marriage or parenthood relative to those with no schooling. Urban residence also delays entry into sexual activity, marriage and parenthood at the bivariate level. However, once education is controlled for, the effect of residence reverses – that is, urban residence is associated with early transition ages. A combination of national boundaries and cultural groupings explain more of the variation in transition rates than either grouping alone. Thus, we conclude that both national and cultural factors appear to influence family transitions in Latin America, in addition to the effects of education and urbanisation. Copyright © 2002 John Wiley & Sons, Ltd.
A new fast block matching algorithm based on complexity‐distortion optimization
Authors: Tai Pol Lin , Liu Chii Tung , Wang Jia Shung 
Published: August 2002

AbstractMost fast block matching algorithms ignore the efficiency in motion compensation within each checking step. In order to achieve better‐compensated performance, the limited computational complexity should be allocated more carefully into each block. It means that the fast block matching algorithm can be viewed as a kind of rate‐distortion optimization problem. The complexity‐distortion optimal fast block matching algorithm should find the maximized quality of the compensated image under a target computational complexity. In order to approach the optimal complexity‐distortion solution, some strategies are developed. For example, a domination‐based motion vector prediction technique is developed to set the initial motion vector for each block. A predictive complexity‐distortion benefit list is established to predict the compensated benefit for each block. Also, a three‐level pattern searching is employed to check the candidate motion vector. Experimental results show that our proposed algorithm outperforms significantly the three‐step search. For example, in “Salesman,” the average checkpoints for one block is 33 by using the three‐step search. The average checkpoint is 1.75 by using our proposal algorithm under the same average PSNR condition. © 2002 Wiley Periodicals, Inc. Int J Imaging Syst Technol 12, 63–67, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ima.10012