bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid turnover of cell‐cycle regulators found in Mirk/dyrk1B transfectants
Authors: Ewton Daina Z. , Lee Kangmoon , Deng Xiaobing , Lim Seunghwan , Friedman Eileen 
Published: December 2002

AbstractMirk/dyrk1B is an arginine‐directed protein kinase, which functions as a transcriptional activator and mediates serum‐free growth of colon carcinoma cells by an unknown mechanism. We now report that turnover of the cdk inhibitor p27kip1 and the G1‐phase cyclin cyclin D1 is enhanced in each of 4 Mirk stable transfectants compared to vector control transfectants and Mirk kinase‐inactive mutant transfectants. This enhanced turnover is proteasome‐dependent and leads to lower protein levels of both p27kip1 and cyclin D1. Lower protein levels of the cdk inhibitor p21cip1 were also observed in the 4 Mirk stable transfectants. Mirk did not alter the activity of a p27kip1 promoter construct or p27kip1 mRNA levels by stable expression, indicating that the decrease in p27kip1 protein levels was due to a posttranscriptional mechanism. These data are consistent with mirk enhancing the expression of some component common to the proteolysis of both p27kip1 and cyclin D1. © 2002 Wiley‐Liss, Inc.
Angioimmunoblastic T cell lymphoma is derived from mature T‐helper cells with varying expression and loss of detectable CD4
Authors: Lee Seung‐Sook , Rüdiger Thomas , Odenwald Tobias , Roth Sabine , Starostik Petr , Müller‐Hermelink Hans Konrad 
Published: December 2002

AbstractAngioimmunoblastic T cell lymphoma (AILT) is a rare lymphoma that is regarded as a clinicopathologic entity but shows considerable histomorphologic diversity, variable immunophenotypes and inconsistent T cell receptor (TCR) gene rearrangement. One hundred four paraffin blocks of AILT were investigated defining tumor cell lineage by triple immunostains with a confocal laser scanning microscope and correlating morphology, immunophenotype and TCRγ gene rearrangement to clinical outcome. Ninety‐nine cases were CD4+, some of them showing a mixture of CD4+ and CD4− tumor cells. The remaining 5 specimens were CD3+/CD4−/CD8−. A considerable number of T cells of different subtypes could always be found, but even in 13 cases predominated by CD8+ cells, proliferation could be attributed to atypical CD4+ cells. TCRγ gene rearrangement was monoclonal in 48 cases (69%) among 70 tested. In 29 of these semi‐quantitative gene scan analysis resulted in a median proportion of monoclonal peak of 35% of PCR‐products. Clinical outcome was identical grouping patients by clonality of TCRγ, absence or presence of clear cell clusters and international prognostic index. We conclude that AILT is mainly derived from CD2+CD3+CD4+CD5+CD7− mature T‐helper cells with varying expression and partial loss of detectable CD4. A significant number of non‐neoplastic T cells (resting CD4+ T cells and activated small or medium‐sized CD8+ lymphocytes) may coexist with a minor neoplastic T cell population. Clinicopathologic correlation suggests AILT to be a well defined homogeneous entity with poor prognosis. Currently no prognostic factors can be derived. © 2002 Wiley‐Liss, Inc.
Familial risk of cancer by site and histopathology
Authors: Hemminki Kari , Li Xinjun 
Published: December 2002

AbstractFamilial risks for histopathology‐specific cancers have not been determined. We used the nationwide Swedish Family‐Cancer Database on 10.2 million individuals and 1 million tumors to calculate standardized incidence ratios (SIRs) for familial cancers of specific histology and morphology among 0‐ to 66‐year‐old offspring. We used histology codes for both offspring and parents, but because of the limited number of cases, the morphology‐specific classification could be used only for offspring by all site‐specific cancers in parents, resulting in inflated risk estimates. A number of novel findings emerged in the histopathology‐specific analysis of familial risks, in addition to some known associations. Overall, specific histology showed an SIR of 2.07 for all cancers compared to an SIR of 2.00 for any histology. However, the small effect was due to breast and prostate cancers, which showed a negligible effect of specific histology. Familial risks of over 4.0 were found for serous papillary cystadenocarcinoma of the ovary, papillary thyroid cancer and low‐grade astrocytoma. Familial risks of over 3.0 were found for signet‐ring gastric cancer, various forms of ovarian cancer and squamous cell skin cancer. Also noteworthy were familial risks of hepatocellular carcinoma (2.48), pancreatic adenocarcinoma (1.92), large cell carcinoma and adenocarcinoma of the lung (2.29 and 2.18, respectively) and clear cell carcinoma of the kidney (2.73). Many of the findings were novel and could be revealed only by applying codes for specific histopathology. These data call for a closer description of familial aggregations and probing for the underlying genetic mechanisms. © 2002 Wiley‐Liss, Inc.
Expression of cyclooxygenase‐2 and peroxisome proliferator‐activated receptor‐γ and levels of prostaglandin E2 and 15‐deoxy‐Δ12,14‐prostaglandin J2 in human breast cancer and metastasis
Authors: Badawi Alaa F. , Badr Mostafa Z. 
Published: December 2002

AbstractCyclooxygenase‐2 (COX‐2) expression and peroxisome proliferator‐activated receptor‐γ (PPARγ) inactivation are linked to increased risk of human breast cancer. The purpose of our study was to examine the relationship between COX‐2 (with the resulting prostaglandins E2, PGE2) and PPARγ (and its natural endogenous ligand 15‐Deoxy‐Δ12,14‐prostaglandin J2, 15d‐PGJ2) at various stages during the development of human breast cancer and its progression to metastasis. Human breast tissue specimens were collected from normal breasts or from individuals with fibrocystic disease and served as controls (n = 22). Tissues were also collected from uninvolved (n = 25), tumor (n = 25) and lymph node metastasis (n = 15) regions from breast cancer patients. COX‐2 and PPARγ mRNA expression were increased and downregulated, respectively, in tissues from cancer patients compared to controls. Metastatic tissues tended to have higher alterations compared to non‐metastatic tissues (p < 0.05). These altered expressions in COX‐2 and PPARγ were paralleled by increases in the tissue levels of PGE2 and decreases in 15d‐PGJ2. A significant inverse correlation was found between PGE2 and 15‐d‐PGJ2 (r = −0.51, p < 0.05). Significant correlations (p < 0.05) were also obtained between COX‐2 and PPARγ mRNA (inverse, r = −0.72) and between COX‐2 and PGE2 (direct, r = 0.68). Increases in COX‐2 mRNA expression and levels of PGE2 and down‐regulation of PPARγ mRNA expression and 15d‐PGJ2 levels were characterized as predictors of breast cancer risk (p < 0.05). Our results suggest that the altered expression of COX‐2 and PPARγ and the subsequent modulation in the tissue levels of PGE2 and 15‐d‐PGJ2 may influence the development of human breast cancer and its progression to metastasis. © 2002 Wiley‐Liss, Inc.
Protein phosphatase‐2A restricts migration of Lewis lung carcinoma cells by modulating the phosphorylation of focal adhesion proteins
Authors: Young M. Rita I. , Liu Shirley W. , Meisinger Jeremy 
Published: December 2002

AbstractCompared to metastatic Lewis lung carcinoma (LLC) cells, nonmetastatic LLC cells have increased levels of activity of the protein phosphatase PP‐2A, which functions to limit their migration through transwell chambers. Inhibition of PP‐2A in nonmetastatic LLC stimulates their transmigration to levels similar to those of metastatic LLC cells. Studies to define the signaling pathways intermediate between diminished PP‐2A activity and stimulated migration showed that inhibiting PP‐2A activity resulted in paxillin serine hyperphosphorylation and tyrosine dephosphorylation. Paxillin was important for the stimulated migration because the increased transmigration in response to PP‐2A inhibition was dampened by expression of mutant paxillin at the LIM3 S457 and S481 residues. Inhibition of PP‐2A also led to the dissolution of FAK/Src/paxillin focal adhesion complexes, which was also dependent on paxillin S457 and S481 residues. In addition, inhibition of PP‐2A resulted in dephosphorylation of Src inhibitory Y527 residue, suggesting increased Src activity. The stimulated transmigration of cells with diminished PP‐2A was in part dependent on this Src activity. These studies show the importance of PP‐2A in limiting tumor cell migration through its modulation of proteins of the focal adhesions. © 2002 Wiley‐Liss, Inc.
Polycystic kidney and renal cell carcinoma in Japanese and Chinese toad hybrids
Authors: Masahito Prince , Nishioka Midori , Kondo Yasuyuki , Yamazaki Ieharu , Nomura Kimie , Kato Yo , Sugano Haruo , Kitagawa Tomoyuki 
Published: December 2002

AbstractFrequent development of renal cell carcinomas in hybrids between Japanese toads (Bufo japonicus) and imported Chinese toads (Bufo raddei) was first reported by 2 of our authors in 1987. Such renal tumors of toads had never been observed previously in the laboratory. To confirm the observation and to establish a new animal model system, hybrids between female Japanese and male Chinese toads were newly generated from 3 pairs of parents and pathological changes in their kidneys were examined sequentially over 6 years. In hybrids from 2 of the 3 pairs, bilateral polycystic kidney developed at a high frequency from 3 months after fertilization, this being associated with the emergence of atypical, premalignant‐appearing cells in proximal tubules. Papillary lesions developed after 12 months and renal cell carcinomas after 48 months. Such pathological changes were never seen in non‐hybrid Chinese or Japanese toads. Electron microscopy showed no evidence of any viral participation. This unique toad model may prove useful for investigation of the underlying mechanisms of genetically determined renal cell carcinogenesis. © 2002 Wiley‐Liss, Inc.
Tumor regression mechanisms by IL‐13 receptor–targeted cancer therapy involve apoptotic pathways
Authors: Kawakami Mariko , Kawakami Koji , Puri Raj K. 
Published: December 2002

AbstractIL‐13 cytotoxin, composed of IL‐13 and a truncated form of Pseudomonas exotoxin, targets IL‐13R‐overexpressing tumor cell lines in vitro and in vivo. To reveal the molecular mechanism of IL‐13 cytotoxin–induced cell death in vivo, we demonstrate activation of apoptotic pathways in 2 s.c. growing human SCCHN tumor models in immunodeficient mice after i.t. administration of IL‐13 cytotoxin. Treatment of HN12 tumor bearing mice with i.p. or i.t. administration of IL‐13 cytotoxin mediated marked regression of established tumors with complete remission. Interestingly, after a single i.t. administration, IL‐13 cytotoxin disappeared within 6 hr but accumulation of caspase‐3, ‐8 and –9 and cleavage of procaspase‐3 and PARP continued within the tumors for a prolonged period. We further demonstrate that IL‐13 cytotoxin also utilizes an alternate pathway of cell death via the release of cytochrome c from mitochondria to the cytosol. Our results indicate that IL‐13 cytotoxin induces 2 major pathways of apoptosis, which may play a role in tumor regression. In addition, apoptotic molecules may serve as surrogate molecular markers of tumor response to IL‐13R‐directed cytotoxin therapy. © 2002 Wiley‐Liss, Inc.
Potentiation of radiation‐induced regrowth delay by isosorbide dinitrate in FSaII murine tumors
Authors: Jordan Bénédicte F. , Beghein Nelson , Aubry Marianne , Grégoire Vincent , Gallez Bernard 
Published: December 2002

AbstractOxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities such as conventional radiotherapy and chemotherapy. Since tumor perfusion is directly affected by the vascular resistance to flow of vessels feeding the tumor, vasodilator drugs might be a way to increase tumor blood flow and oxygenation. The effects of nitric oxide (NO) donor administration on tumor oxygenation, perfusion and radiation sensitivity were studied in the FSaII tumor model. Local tumor oxygenation was measured using electron paramagnetic resonance oximetry and a fiberoptic probe, OxyLite. We concomitantly measured the modulation of tumor blood flow by laser Doppler flowmetry. We determined FSaII tumor regrowth delay after isosorbide dinitrate administration and irradiation compared to carbogen breathing before irradiation and with X‐rays alone. Administration of the NO donor improved the FSaII tumor pO2 concomitant with an increase in tumor blood flow. We also demonstrated an increase in FSaII tumor radiation sensitivity after isosorbide dinitrate administration, which was similar to the effect of carbogen breathing in the same tumor model. Administration of isosorbide dinitrate could be considered in terms of improvement in tumor blood flow and a possible concomitant increase in accessibility of chemosensitizing agents to the tumor, particularly in terms of modification of the tumor response to irradiation. © 2002 Wiley‐Liss, Inc.
Modulation of P‐glycoprotein but not MRP1‐ or BCRP‐mediated drug resistance by LY335979
Authors: Shepard Robert L. , Cao Jin , Starling James J. , Dantzig Anne H. 
Published: December 2002

AbstractOur study examines the ability of LY335979 (Zosuquidar trihydrochloride) to modulate 3 distinct ABC transporters that are mechanisms of drug resistance: P‐glycoprotein (Pgp, ABCB1), multidrug resistance associated protein (MRP1, ABCC2) and breast cancer resistance protein (BCRP, ABCG2). Pgp‐mediated resistance can be modulated by coadministration with the highly potent, selective inhibitor, LY335979. Modulation of resistance by mitoxantrone and vinorelbine, 2 drugs used to treat certain solid tumors, was examined in a 3‐day cytotoxicity assay using a panel of HL60 leukemia cell lines or MCF‐7 breast cancer transfectants. LY335979, at 0.5 μM, substantially reversed mitoxantrone resistance and fully reversed vinorelbine resistance of Pgp‐expressing HL60/Vinc cells. However, LY335979 did not modulate drug resistance in the MRP1‐expressing HL60/ADR or drug‐sensitive parental HL60 cells. To ascertain if LY335979 modulates BCRP‐mediated drug resistance, the sensitivity of 26‐fold mitoxantrone resistant, BCRP‐transfected MCF‐7 cells was evaluated. Addition of 5 μM LY335979, a concentration ∼100‐fold higher than the affinity of Pgp, had little to no effect on the BCRP transfectant. [125I]Iodomycin photolabeled Pgp in CEM/VLB100 membranes and was inhibited by 5 μM LY335979 and GF120918. No photolabeling of MRP or BCRP occurred in H69AR or MCF‐7/BCRP membranes, respectively. These results further demonstrate that LY335979 is highly specific for Pgp and does not modulate MRP1‐ or BCRP‐mediated resistance and can be used in combination with mitoxantrone and vinorelbine in tumor cells. © 2002 Wiley‐Liss, Inc.
Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism
Authors: Wang Lizhong , Habuchi Tomonori , Mitsumori Kenji , Li Zhenhua , Kamoto Toshiyuki , Kinoshita Hidefumi , Tsuchiya Norihiko , Sato Kazunari , Ohyama Chikara , Nakamura Akira , Ogawa Osamu , Kato Tetsuro 
Published: December 2002

AbstractCCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single‐nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1
A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13–3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09–3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65–1.54, BPH: aOR = 0.91, 95% CI 0.60–1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38–6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44–2.34). No significant difference in genotype frequency was found among patients with low‐, intermediate‐ and high‐grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high‐grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1
A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2‐fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects. © 2002 Wiley‐Liss, Inc.
Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non‐small cell lung cancer
Authors: Nakamura Haruhiko , Saji Hisashi , Ogata Akihiko , Hosaka Makoto , Hagiwara Masaru , Kawasaki Norihito , Kato Harubumi 
Published: December 2002

AbstractThe HER2 oncogene, which encodes the tyrosine kinase receptor, is commonly overexpressed in several types of cancer. Treatment using a humanized monoclonal antibody bound to HER2 product is becoming standard therapy for advanced breast cancer. Overexpression occurs in approximately 30% of non‐small cell lung cancers (NSCLCs) and has been associated with poor prognosis. However, the frequency of a genetic aberration in the HER2 gene in lung cancer and the association between gene amplification and prognosis are poorly defined. To clarify these relationships, we simultaneously analyzed protein overexpression by immunohistochemistry (IHC) and determined the gene copy number by FISH in 50 surgical specimens of NSCLC. A low‐grade increase in the copy number (3 to 8 copies) of the HER2 gene was detected in 44% of tumors. Most represented polysomy of chromosome 17. Protein overexpression was observed in 26%. Overexpression was detected in adenocarcinoma more frequently than in squamous cell carcinoma. No significant correlation was observed between copy number increase and overexpression. Neither gene copy number increase nor overexpression correlated with survival. We conclude that the significance of HER2 status in NSCLC is different from that in breast cancer because high‐grade amplification occurs rarely. © 2002 Wiley‐Liss, Inc.
Circulating anti‐MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer
Authors: Hamanaka Yuichiro , Suehiro Yutaka , Fukui Mikiko , Shikichi Kyoko , Imai Kohzoh , Hinoda Yuji 
Published: December 2002

AbstractMUC1 is immunogenic in vivo and humoral and cellular immune responses against MUC1 have been detected in cancer patients. Our study explored the association of circulating anti‐MUC1 antibodies with clinicopathological parameters or patients' survival of pancreatic cancer. Serum specimens from 36 patients with invasive ductal carcinoma of the pancreas were subjected to enzyme immunoassay for anti‐MUC1 IgG or IgM antibodies. Serum levels of anti‐MUC1 IgG antibodies were significantly correlated with survival time (p = 0.0004), whereas neither those of anti‐MUC1 IgM nor anti‐Galα(1,3)Gal IgG antibodies, the latter known as natural antibodies cross‐reactive with MUC1, showed a given tendency. Some patients' sera with the higher antibody titer showed the reactivity with MUC1‐transfectants of cultured pancreatic cancer cells, but not with MUC1‐negative parental cells. When the samples were tentatively divided into 2 groups by the serum level of anti‐MUC1 IgG antibodies, the survival of patients was significantly longer in the group with optical density ≥0.3 than in that with optical density <0.3 (p = 0.008). Circulating anti‐MUC1 IgG antibody levels remained significant (HR, 0.03; 95% CI, 0.003–0.289; p = 0.0024) after multivariate analysis for pTNM stage, patient age and gender. These data suggest that circulating anti‐MUC1‐IgG antibody levels may be predictive for survival of pancreatic cancer patients. © 2002 Wiley‐Liss, Inc.
Fabrication and measurement of a microstrip‐array antenna for the electronic toll collection system (ETCS)
Authors: Yoon JoongHan , Kwak KyungSup 
Published: December 2002

AbstractThis paper describes the design, fabrication, and measurement of a sequential‐rotation microstrip‐array antenna for the Electronic Toll Collection System (ETCS). The ETCS is made possible by using roadside equipment with a radiation pattern that can accurately pinpoint the designated communication area, without interference from other lanes. The sequential‐rotation microstrip‐array antenna is designed and applied to the absorber to reduce the side lobe level (SLL) for the ETCS antenna. Results show that the antenna yields a return loss at a center frequency of −20.675 dB, an axial ratio of 1.15 dB, and a gain of 20.26 dBi. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 77–79, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10678
Image reconstruction of two‐dimensional objects inside dielectric walls
Authors: Lu C. C. , Zhong X. G. 
Published: December 2002

AbstractThis paper discusses a special imaging reconstruction problem in which the object to be reconstructed resides in a homogeneous media but consists of a known part and an unknown part. The known part is combined with the homogeneous background media to form an inhomogeneous media. The dielectric permittivity profiles are reconstructed for the unknown part using the Born iteration (BI) method. Numerical examples demonstrate that this modified BI algorithm has faster convergence and higher accuracy than the regular BI method. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 91–95, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10684
Characteristic basis function method: A new technique for efficient solution of method of moments matrix equations
Authors: Prakash V. V. S. , Mittra Raj 
Published: December 2002

AbstractIn this paper, we introduce a novel approach for an efficient solution of matrix equations arising in the method of moments (MoM) formulation of electromagnetic scattering problems. This approach is based on the characteristic basis functions (CBFs), which are used to substantially reduce the matrix size because these bases are not bound by the conventional λ/20 domain discretization. As a result, it is possible to electrically solve large problems with much fewer unknowns than those needed when using conventional RWG basis functions. The accuracy and efficiency of the CBFs are demonstrated in a variety of scattering problems to illustrate the versatility of the approach. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 95–100, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10685