bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers
Authors: Adem Camilo , Reynolds Carol , Soderberg Cheryl L. , Slezak Jeffrey M. , McDonnell Shannon K. , Sebo Thomas J. , Schaid Daniel J. , Myers Jeffrey L. , Sellers Thomas A. , Hartmann Lynn C. , Jenkins Robert B.
Published: December 2002

BACKGROUND

BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions.

METHODS

The authors developed two case cohorts of high‐risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB‐1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort.

RESULTS

The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22–33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB‐1 proliferation indices compared with other patients with and without a family history of breast carcinoma.

CONCLUSIONS

The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women. Cancer 2003;97:1–11. © 2003 American Cancer Society.

DOI 10.1002/cncr.11048
Energy restriction early in life and colon carcinoma risk
Authors: Dirx Miranda J. M. , van den Brandt Piet A. , Goldbohm R. Alexandra , Lumey L. H.
Published: December 2002

BACKGROUND

This study evaluated the effects of severe undernutrition during adolescence and subsequent colon carcinoma risk.

METHODS

The authors evaluated The Netherlands Cohort Study on Diet and Cancer (NLCS) among 62,573 women and 58,279 men aged 55–69 years at baseline. Information on diet and risk factors was collected by questionnaire in 1986. Additional information was collected concerning residence during the hunger winter (1944–1945), the World War II years (1940–1944), and father's employment status during the economic depression of 1932–1940, which were used as indicators of exposure. After 7.3 years of follow‐up, 807 colon carcinoma cases (388 females and 419 males) were available for analysis.

RESULTS

Multivariate analysis showed that both men and women who had lived in a western city in 1944–1945 had a decreased colon carcinoma risk (men: relative risk [RR] = 0.85, 95% confidence interval [CI] = 0.62–1.16; women: RR = 0.80, 95%CI = 0.59–1.09). No association between colon carcinoma risk and urban versus rural residence was found during the war years (1940–1944). Having an unemployed father during the economic depression (1932–1940) was also associated with a small decrease in colon carcinoma risk for men (RR = 0.90, 95% CI =0.62–1.31) and women (RR = 0.75, 95%CI 0.49‐1.14). In subgroup analyses, a decreased colon carcinoma risk for men and women who were in their adolescent growth spurt and living in a western city during the hunger winter of 1944–1945 was noted (men: RR = 0.72, 95% CI = 0.31–1.65; women: RR = 0.88, 95% CI = 0.40–1.96). No associations were statistically significant because of the limited study size.

CONCLUSIONS

In the current study, a weak inverse relation was found between energy restriction early in life and subsequent colon carcinoma risk for men and women. However, these findings need replication in a larger study. Cancer 2003;97:46–55. © 2003 American Cancer Society.

DOI 10.1002/cncr.11052
Optimal distribution of linear control intensity over the frequency range
Authors: Corbi Ottavia
Published: December 2002

In this paper, a control strategy for structural systems is proposed and developed in the frequency domain. The algorithm is substantially based on a linear derivative feedback and a convolution of the control parameter, whose distribution in the frequency field is chosen in such a manner as to comply with the requirements of an ad hoc formulated constrained optimum problem, with the response data monitored until the instant of control action application. Some numerical testing is carried out by referring to given recorded accelerograms, showing a good performance of the proposed approach. Copyright © 2002 John Wiley & Sons, Ltd.
A neural network approach for structural identification and diagnosis of a building from seismic response data
Authors: Huang C. S. , Hung S. L. , Wen C. M. , Tu T. T.
Published: December 2002

This work presents a novel procedure for identifying the dynamic characteristics of a building and diagnosing whether the building has been damaged by earthquakes, using a back‐propagation neural network approach. The dynamic characteristics are directly evaluated from the weighting matrices of the neural network trained by observed acceleration responses and input base excitations. Whether the building is damaged under a large earthquake is assessed by comparing the modal parameters and responses for this large earthquake with those for a small earthquake that has not caused this building any damage. The feasibility of the approach is demonstrated through processing the dynamic responses of a five‐storey steel frame, subjected to different strengths of the Kobe earthquake, in shaking table tests. Copyright © 2002 John Wiley & Sons, Ltd.
Localization analysis in softening RC frame structures
Authors: Khaloo Ali R. , Tariverdilo Saeed
Published: December 2002

This paper discusses the sensitivity of softening reinforced concrete frame structures to the changes in input ground motion and investigates the possibility of localizations for this type of structure in static and dynamic analysis. A finite element model is used in which the sections resisting force are calculated using a proposed differential hysteretic model. This model is especially developed for modelling softening behaviour under cyclic loading. To obtain parameters of the differential model the moment–curvature of each section is evaluated using a microplane constitutive law for concrete and bi‐linear elasto‐plastic law for reinforcements. The capability of the procedure is verified by comparing results with available experimental data at element level, which shows good accuracy of the procedure. The effect of possible changes in ground motion is assessed using a non‐stationary Kanai–Tajimi process. This process is used to generate ground motions with approximately the same amplitude and frequency content evolution as those of base ground motion. The possibility of localization in static and dynamic loading is investigated using two structures. A measure for the possibility of localization in code‐designed structures is obtained. This study indicates that localization may occur in ordinary moment‐resisting structures located in high seismic zones. Localization may result in substantial drift in global response and instability due to P–δ effect. Also, it is shown that the structure becomes very sensitive to the input ground motion. It is concluded that allowance by some design codes of the use of ordinary moment‐resisting frames in regions with high seismicity should be revised or improvements should be made in the detailing requirements at critical sections of these structures. Copyright © 2002 John Wiley & Sons, Ltd.
Optimal maintenance strategies for structures in seismic zones
Authors: Montes‐Iturrizaga R. , Heredia‐Zavoni E. , Esteva L.
Published: December 2002

In this paper an approach is developed for establishing optimal maintenance (repair) strategies of structures in seismic zones. The approach is based on expected future costs and the main decision variable is a damage threshold for repair given an acceptable reliability level. It is considered that structural damage accumulates over a number of earthquakes until a threshold is reached or exceeded, after which the structure is repaired so that there is no remaining damage. A Markov model is implemented for such a process of damage accumulation during future earthquakes. An algorithm is proposed for computing non‐linear structural response to earthquakes using a damage function model. This algorithm is used to evaluate transition probabilities between damage states based on simulations of future earthquakes of given intensities. Expressions are derived for evaluating expected life‐cycle damage costs and structural reliability as a function of time and of the damage threshold for repair. As an application, a single‐degree‐of‐freedom structural system is studied. In addition, the paper addresses the case of instrumented structures where information from earthquake response records is available. Such information is incorporated into the formulation for maintenance strategies by means of a Bayesian approach for updating the probability distribution of structural damage and of non‐linear behaviour parameters so that predictions about costs and reliability are improved. Copyright © 2002 John Wiley & Sons, Ltd.
The rocking spectrum and the limitations of practical design methodologies
Authors: Makris Nicos , Konstantinidis Dimitrios
Published: December 2002

This paper is concerned with the superficial similarities and fundamental differences between the oscillatory response of a single‐degree‐of‐freedom (SDOF) oscillator (regular pendulum) and the rocking response of a slender rigid block (inverted pendulum). The study examines the distinct characteristics of the rocking spectrum and compares the observed trends with those of the response spectrum. It is shown that the rocking spectrum reflects kinematic characteristics of the ground motions that are not identifiable by the response spectrum. The paper investigates systematically the fundamental differences in the dynamical structure of the two systems of interest and concludes that rocking structures cannot be replaced by ‘equivalent’ SDOF oscillators. The study proceeds by examining the validity of a simple, approximate design methodology, initially proposed in the late 1970s and now recommended in design guidelines to compute rotations of slender structures by performing iteration either on the true displacement response spectrum or design spectrum. This paper shows that the simple design approach is inherently flawed and should be abandoned, in particular for smaller, less‐slender blocks. The study concludes that the exact rocking spectrum emerges as a distinct intensity measure of ground motions. Copyright © 2002 John Wiley & Sons, Ltd.
The effects of repeated earthquake ground motions on the non‐linear response of SDOF systems
Authors: Amadio C. , Fragiacomo M. , Rajgelj S.
Published: December 2002

In many parts of the world, the repetition of medium–strong intensity earthquake ground motions at brief intervals of time has been observed. The new design philosophies for buildings in seismic areas are based on multi‐level design approaches, which take into account more than a single damageability limit state. According to these approaches, a sequence of seismic actions may produce important consequences on the structural safety. In this paper, the effects of repeated earthquake ground motions on the response of single‐degree‐of‐freedom systems (SDOF) with non‐linear behaviour are analysed. A comparison is performed with the effect of a single seismic event on the originally non‐damaged system for different hysteretic models in terms of pseudo‐acceleration response spectra, behaviour factor q and damage parameters. The elastic–perfect plastic system is the most vulnerable one under repeated earthquake ground motions and is characterized by a strong reduction of the q‐factor. A moment resisting steel frame is analysed as well, showing a reduction of the q‐factor under repeated earthquake ground motions even larger than that of an equivalent SDOF system. Copyright © 2002 John Wiley & Sons, Ltd.
A pseudo‐force iterative method with separate scale factors for dynamic analysis of structures with non‐proportional damping
Authors: Lin Feng‐Bao , Wang Yung‐Kuo , Cho Young S.
Published: December 2002

Dynamic equilibrium equations of structural systems with non‐proportional damping are coupled through the damping terms. Such coupling invalidates application of the classical modal superposition method. In this paper, a mode‐superposition pseudo‐force method is proposed. The coupled equilibrium equations are solved by an iterative process in which the coupling terms are treated as pseudo‐forces. A scale factor for each mode of the system is obtained by optimizing the iteration convergence. Through these uniquely solved scale factors, the modified modal equations not only converge much faster but also yield results with higher accuracy. A proof of the convergence of the iterative process is also presented. Copyright © 2002 John Wiley & Sons, Ltd.
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

Mirk/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

Angioimmunoblastic 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

Familial 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

Cyclooxygenase‐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

Compared 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

Frequent 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

IL‐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

Oxygen 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

Our 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

CCND1 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

The 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

MUC1 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

This 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

This 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

In 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
Analysis of two‐concentric annular ring microstrip antenna
Authors: Kanaujia Binod K. , Vishvakarma Babau R.
Published: December 2002

The analysis of a two‐concentric annular ring patch antenna using planar waveguide model is presented. Consequently, various parameters such as input impedance (Zin), VSWR, return loss, resonance frequency, and radiation patterns have been theoretically investigated as a function of gap length and feed location. The various parameters of the two‐concentric annular ring patch antenna are found to depend heavily on gap length and feed locations. The radiated power and 3‐dB beamwidth improve significantly, as compared to a single radiator. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 104–108, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10688
The effect of shutter thickness on opto‐mechanical variable optical attenuators
Authors: Khalil D. , Maaty H. , Bashir A. , Saadany B.
Published: December 2002

In this work, we study the effect of shutter thickness on the optical attenuation of an opto‐mechanical variable optical attenuator (VOA). Both experimental and simulation results show maximum shutter displacement in the received optical field, which increases with larger shutter thickness. This behaviour has not been reported or analysed previously. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 110–112, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10690
Investigation of input power dynamic range enhancement of a cross‐phase modulation wavelength converter by pre‐amplification
Authors: Jeon Yong‐Soo , Kang Jeung‐Mo , Kim Tae‐Young , Han Sang‐Kook , Lee Seok
Published: December 2002

The performance of a pre‐amplified cross‐phase modulation (XPM) wavelength converter has been theoretically investigated. We showed that the pre‐amplifier enhances the input optical power dynamic range by 3 dB. The additional 4‐dB improvement of the power penalty in wavelength conversion obtained through BER simulation shows that integrating a pre‐amplifier enables the accommodation of a relatively small input optical power. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 131–134, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10697
A 1.2‐V fully integrated 2.4‐GHz low‐noise amplifier in 0.35‐μm CMOS technology
Authors: Meng C. C. , Chiang M. H. , Wu T. H.
Published: December 2002

A 1.2‐V fully integrated 0.35‐μm inductively degenerated common source CMOS low‐noise amplifier has been demonstrated at 2.4 GHz in this paper. A simple common source configuration can be operated at lower voltage and has lower output impedance when compared with a conventional high output impedance cascode LNA circuit topology. The input matching inductance, output matching inductance, and source degeneration inductance are integrated on a single chip. The fully integrated 2.4‐GHz CMOS LNA has 5.27‐dB power gain, 17‐dB input return loss, 15‐dB output return loss, 4‐dB noise figure, and −1‐dBm IIP1dB and 8‐dBm IIP3 at Vdd = 1.2 V and Idd = 10 mA, respectively. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 136–139, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10699
Surface heat flow, crustal temperatures and mantle heat flow in the Proterozoic Trans‐Hudson Orogen, Canadian Shield
Authors: Rolandone F. , Jaupart C. , Mareschal J. C. , Gariépy C. , Bienfait G. , Carbonne C. , Lapointe R.
Published: December 2002

The Paleo‐Proterozoic (1.8 Ga) Trans‐Hudson Orogen (THO), of intermediate age between the Superior (2.7 Ga) and Grenville (1.0 Ga) provinces, is located near the center of the Canadian Shield. We report on new measurements of heat flow and radiogenic heat production in 30 boreholes at 17 locations in this province. With these data, reliable values of heat flow and heat production are available at 45 sites in the THO. The mean and standard deviation of heat flow values are 42 ± 9 mW m−2. In this province, distinctive geological domains are associated with specific heat flow distributions. The heat flow pattern follows the surface geology with a central area of low values over an ancient back arc basin (Kisseynew) and an ancient island arc (Lynn Lake Belt) made of depleted juvenile rocks. Higher heat flow values found in peripheral belts are associated with recycled Archean crust. Within the Canadian Shield, there is no significant variation in heat flow as a function of age between provinces spanning about 2 Gyr. There is no geographic trend in heat flow across the Canadian Shield from the THO to the Labrador Sea. Low heat flow areas where the crustal structure is well‐known are used to determine an upper bound of 16 mW m−2 for the mantle heat flow. Present and paleogeotherms are calculated for a high heat flow area in the Thompson metasedimentary belt. The condition that melting temperatures were not reached in Proterozoic times yields a lower bound of 11–12 mW m−2 for the mantle heat flow.
Mars' upper atmosphere and ionosphere at low, medium, and high solar activities: Implications for evolution of water
Authors: Krasnopolsky Vladimir A.
Published: December 2002

Self‐consistent models for 11 neutral and 18 ion species from 80 to 300 km on Mars have been developed by solving the continuity equations including ambipolar diffusion for ions. The models were calculated for the conditions of the HST, FUSE, and Mariner 6 and 7 observations of D, H2, and H, respectively, when the solar activity index was equal to 25, 61, and 88 at Mars orbit, respectively. Special care was taken to simulate the processes of H2 and HD dissociation in the reactions with CO2+, O+, CO+, N2+, N+, Ar+, and O(1D) and by photoelectrons. Thermal and nonthermal escape velocities were used as the upper boundary conditions for H2, H, HD, D, and He. The H2 and HD mixing ratios of 15 ppm and 11 ppb chosen to fit the FUSE and HST observations of H2 and D, respectively, result in (HD/H2)/(HDO/H2O) = 0.4. This value agrees with the depletion of D in H2 because of the smaller HDO photolysis cross section and the preferential condensation of HDO above the condensation level. Therefore the controversial problem of deuterium fractionation is solved throughout the atmosphere. The influx of cometary water was ≈0.5 m planetwide in the last 3.8 billion years. It cannot affect the estimates of more than 30 m of water lost by sputtering and nonthermal and thermal escape and more than 1.3 km of water lost in the reaction with iron with subsequent hydrodynamic escape of H2. The calculated ion density profiles at various solar activity and the column reaction rates provide complete quantitative information for behavior of each ion, its formation, and its loss. The HCO+ ion is abundant in Mars' ionosphere because it is a final product of many reactions of other ions with H2 and does not react with neutral species.
Effects of melting and freezing in the Greenland sea
Authors: Vinje Torgny , Løyning Terje Brinck , Polyakov Igor
Published: December 2002

Ice thickness and drift measurements complemented with modeling results are examined. In the East‐Greenland ice drift stream (EGIS), the ice is thicker at 79°N than at 75°N in winter but similar in summer due to melting, advection, and seasonal changes of the wind pattern in Fram Strait. Ice fluxes at 79°N and 75°N vary coherently. Summer EGIS melting rates exceed 0.5 m/mo. In winter, oceanic currents govern melting/freezing processes. In the western EGIS, exposed to the cold East‐Greenland Current, ice grows. In the eastern EGIS, influenced by warm Atlantic water, ice melts. East of EGIS, in Nordbukta (75–77°N), winter freezing occurs. A topographically controlled cyclonic gyre maintains a divergent Nordbukta ice drift, causing more leads, ocean cooling and ice formation, favoring deep convection. However, stratification in the Greenland Sea Gyre is poorly correlated with Nordbukta ice production, but shows coherent variations with the NAO index.
Slope streaks on Mars: Correlations with surface properties and the potential role of water
Authors: Schorghofer Norbert , Aharonson Oded , Khatiwala Samar
Published: December 2002

The Mars Orbiter Camera on board the Mars Global Surveyor spacecraft has returned images of numerous dark streaks that are the result of down‐slope mass movement occurring under present‐day martian climatic conditions. We systematically analyze over 23,000 high‐resolution images and demonstrate that slope streaks form exclusively in regions of low thermal inertia (confirming earlier results), steep slopes, and, remarkably, only where peak temperatures exceed 275 K. The northernmost streaks, which form in the coldest environment, form preferentially on warmer south‐facing slopes. Repeat images of sites with slope streaks show changes only if the time interval between the two images includes the warm season. Surprisingly (in light of the theoretically short residence time of H2O close to the surface), the data support the possibility that small amounts of water are transiently present in low‐latitude near‐surface regions of Mars and undergo phase transitions at times of high insolation, triggering the observed mass movements.