bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in cortical material properties throughout the human dentate mandible
Authors: Schwartz‐Dabney C.L. , Dechow P.C.
Published: February 2003

Material properties and their variations in individual bone organs are important for understanding bone adaptation and quality at a tissue level, and are essential for accurate mechanical models. Yet material property variations have received little systematic study. Like all other material property studies in individual bone organs, studies of the human mandible are limited by a low number of both specimens and sampled regions. The aims of this study were to determine: 1) regional variability in mandibular material properties, 2) the effect of this variability on the modeling of mandibular function, and 3) the relationship of this variability to mandibular structure and function. We removed 31 samples on both facial and lingual cortices of 10 fresh adult dentate mandibles, measured cortical thickness and density, determined the directions of maximum stiffness with a pulse transmission ultrasonic technique, and calculated elastic properties from measured ultrasonic velocities. Results showed that each of these elastic properties in the dentate human mandible demonstrates unique regional variation. The direction of maximum stiffness was near parallel to the occlusal plane within the corpus. On the facial ramus, the direction of maximum stiffness was more vertically oriented. Several sites in the mandible did not show a consistent direction of maximum stiffness among specimens, although all specimens exhibited significant orthotropy. Mandibular cortical thickness varied significantly (P < 0.001) between sites, and decreased from 3.7 mm (SD = 0.9) anteriorly to 1.4 mm posteriorly (SD = 0.1). The cortical plate was also significantly thicker (P < 0.003) on the facial side than on the lingual side. Bone was 50–100% stiffer in the longitudinal direction (E3, 20–30 GPa) than in the circumferential or tangential directions (E2 or E1; P < 0.001). The results suggest that material properties and directional variations have an important impact on mandibular mechanics. The accuracy of stresses calculated from strains and average material properties varies regionally, depending on variations in the direction of maximum stiffness and anisotropy. Stresses in some parts of the mandible can be more accurately calculated than in other regions. Limited evidence suggests that the orientations and anisotropies of cortical elastic properties correspond with features of cortical bone microstructure, although the relationship with functional stresses and strains is not clear. Am J Phys Anthropol 120:252–277, 2003. © 2003 Wiley‐Liss, Inc.
Peripartum cortisol levels and mother‐infant interactions in Japanese macaques
Authors: Bardi Massimo , Shimizu Keiko , Barrett Gordon M. , Borgognini‐Tarli Silvana M. , Huffman Michael A.
Published: February 2003

As evidence accumulates regarding the influence of hormones and stress‐related conditions on maternal behavior, it becomes critical to better understand the relationship between physiological stress and the ability to cope with infants. Eight Japanese macaque females were observed 3 hr per week during the first 12 weeks after parturition; fecal samples were collected twice a week from each mother, starting 4 weeks before parturition and ending 4 weeks after parturition. Time spent in contact, maternal responsiveness, latency of response, and maternal rejection were measured and correlated with peripartum excreted cortisol and estradiol metabolite levels. Two indices of peripartum hormonal status were also tested against behavior: the postpartum stress index, and the postpartum cortisol/prepartum estradiol ratio (F/E). Postpartum cortisol levels showed a positive correlation with maternal rejection. The cortisol/estradiol ratio was positively correlated with rejection and latency of response, and negatively correlated with maternal responsiveness. Prepartum cortisol levels and the postpartum stress index did not correlate with any aspect of maternal behavior. Our findings suggest that hypothalamic‐pituitary‐adrenal (HPA) axis activity per se is not enough to predict the quality of interaction between mother and infant. Only when cortisol is high relative to estradiol could it be symptomatic of a possible negative feedback response involving stress, adrenal activity, and the ability of mothers to cope with the additional problems imposed by newborns. Am J Phys Anthropol 120:298–304, 2003. © 2003 Wiley‐Liss, Inc.
Patterns of joint size dimorphism in the elbow and knee of catarrhine primates
Authors: Lague Michael R.
Published: February 2003

Differences in body size between conspecific sexes may incur differences in the relative size and/or shape of load‐bearing joints, potentially confounding our understanding of variation in the fossil record. More specifically, larger males may experience relatively greater limb joint stress levels than females, unless an increase in weight‐related forces is compensated for by positive allometry of articular surface areas. This study examines variation in limb joint size dimorphism (JSD) among extant catarrhines to: 1) determine whether taxa exhibit JSD beyond that expected to simply maintain geometric similarity between sexes, and 2) test whether taxa differ in JSD (relative to body size dimorphism) with respect to differences in limb use and/or phylogeny. “Joint size” was quantified for the distal humerus and distal femur of 25 taxa. Analysis of variance was used to test for differences between sexes (in joint size ratios) and among taxa (in patterns of dimorphism). Multiple regression was used to examine differences in JSD among taxa after accounting for variation in body size dimorphism (BSD) and body size. Although degrees of humeral and femoral JSD tend to be the same within species, interspecific variation exists in the extent to which both joints are dimorphic relative to BSD. While most cercopithecoids exhibit relatively high degrees of JSD (i.e., positive allometry), nonhuman hominoids exhibit degrees of JSD closer to isometry. These results may reflect a fundamental distinction between cercopithecoids and hominoids in joint design. Overall, the results make more sense (from a mechanical standpoint) when adjustments to BSD are made to account for the larger effective female body mass associated with bearing offspring. In contrast to other hominoids, modern humans exhibit relatively high JSD in both the knee and elbow (despite lack of forelimb use in weight support). Estimates of BSD based on fossil limb bones will vary according to the extant analogue chosen for comparison. Am J Phys Anthropol 120:278–297, 2003. © 2003 Wiley‐Liss, Inc.
Crystallographic report: Chlorobis(pyrrolinedithiocarbamato)antimony(III)
Authors: Lai Chian Sing , Tiekink Edward R. T.
Published: January 2003

The X‐ray crystal structure of Sb(S2CN(CH2)4)2Cl features a five‐coordinate geometry for antimony within a ClS4 donor set, provides evidence for a stereochemical influence exerted by the lone pair of electrons on antimony, and shows no evidence for molecular aggregation. Copyright © 2003 John Wiley & Sons, Ltd.
Crystallographic report: (4,7‐Diphenyl‐1,10‐phenanthroline) bis(pyrrolinedithiocarbamato)zinc(II) chloroform solvate
Authors: Lai Chian Sing , Tiekink Edward R. T.
Published: January 2003

The mononuclear structure of Zn(S2CN(CH2)4)2(4,7‐Ph2‐1,10‐phenanthroline) shows the zinc atom in each of the two independent molecules comprising the asymmetric unit to exist in a distorted octahedral geometry defined by an N2S4 donor set. Copyright © 2003 John Wiley & Sons, Ltd.
Crystallographic report: Phenyl(N,N‐di‐n‐propyldithiocarbamato)mercury(II)
Authors: Lai Chian Sing , Tiekink Edward R. T.
Published: January 2003

The structure of PhHg(S2CNPr2) shows a distorted linear geometry about mercury defined by a sulfur and a carbon atom. Centrosymmetric molecules aggregate via HgS interactions to form loosely associated dimers. Copyright © 2003 John Wiley & Sons, Ltd.
Alumina‐supported nickel catalyst for liquid‐phase reactions: an expedient and efficient heterogeneous catalyst for hydrogenation reactions
Authors: Jurvilliers Xavier , Schneider Raphaël , Fort Yves , Ghanbaja Jaafar
Published: January 2003

The preparation of a new nickel(0)/Al2O3 catalyst for hydrogenation reactions is described. The nickel(0)/Al2O3 catalysts were prepared by impregnation of alumina with a solution of a nickel(II) salt. After drying, the nickel(II) salt was reduced under mild conditions into nickel(0) using t‐BuONa‐activated sodium hydride in tetrahydrofuran at 65 °C. The nickel(0)/Al2O3 catalysts obtained were characterized by transmission electron microscopy and energy‐dispersive X‐ray spectroscopy. The supported catalysts were successfully used in solution‐phase hydrogenation of double and triple bonds. Although the activity of the nickel(0)/Al2O3 is comparable to non‐supported nickel(0) reagents, it has the advantage of being reusable more than ten times with only a slight decrease of reactivity. Copyright © 2003 John Wiley & Sons, Ltd.
Structure of azo dye organotin(IV) compounds containing a C,N‐chelating ligand
Authors: Růžička Aleš , Lyčka Antonín , Jambor Roman , Novák Petr , Čísařová Ivana , Holčapek Michal , Erben Milan , Holeček Jaroslav
Published: January 2003

Two complexes derived from simple azo dyes (methyl orange and para‐methyl red) and the [(2‐dimethylaminomethyl)phenyl](diphenyl)tin(IV) moiety have been prepared and their NMR, MS, IR, Raman and UV–VIS spectra were measured and X‐ray structures determined. Both compounds reveal the same structure in chloroform and in the solid state. The central tin atoms exist in a slightly distorted trans‐trigonal bipyramidal geometry. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro antitumour activity of some organogermanium radioprotectors
Authors: Célariès Benoît , Gielen Marcel , de Vos Dick , Rima Ghassoub
Published: January 2003

Four germanium derivatives of 2,2′‐oxydiethanethiol and 2,2′‐thiodiethanethiol have been synthesized and characterized by 1H and 13C NMR, mass spectroscopy and elemental analysis. The antitumour activity of one of them is comparable to those of cis‐platin and etoposide. Copyright © 2003 John Wiley & Sons, Ltd.
N‐Germyl derivatives of sulfacetamide and ortho‐(sulfonamido)phenylamines: characterization of N‐[o‐(N′,N′‐dimethylsulfonamido)phenyl]‐N‐dimesitylgermaimine
Authors: Chazalette C. , Khallaayoun A. , Rivière‐Baudet M. , El Baz F.
Published: January 2003

Triethylgermylation of sulfacetamide occurs on the sulfonamido nitrogen in competition with the 1,2 addition of the starting triethylgermyl dimethylamine on the carbonyl group. Thermal decomposition in the presence of dimethylamine yields N‐triethylgermylsulfanilamide. Stable 1:1 sulfacetamide–DBU and 1:1 sulfacetamide–Et3N complexes were isolated and fully characterized in the course of dehydrochlorination reactions. o‐Sulfonamidophenylamine yields N,N′‐bis‐triethylgermylated derivatives, whereas o‐(N,N‐dimethylsulfonamido)phenylamine leads to monogermylated compounds. The N‐dimethylaminodimesitylgermyl derivative is thermally stable. Dehydrohalogenation of the N‐dimesitylfluorogermyl compound leads to the thermally stable but water sensitive N‐[o‐(N′,N′‐dimethylsulfonamido)phenyl]‐N‐dimesitylgermaimine. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis of two novel cobalt complexes and their crystal structures
Authors: Shi Min , Duan Wei‐Liang
Published: January 2003

Two new cobalt complexes were successfully synthesized from the reaction of binaphthyl Schiff base 2 with Co(OAc)2 in the presence of sodium methoxide at 80 °C for 24 h and Co(acac)3 in toluene under reflux. Their unique crystal structures are unambiguously disclosed by X‐ray analysis. Complex 3 is triclinic, space group P1, unit cell dimensions a = 10.742(2) Å, b = 11.153(2) Å, c = 12.715 Å, α = 79.865(3) °, β = 76.053 °, γ = 72.532(4) °, volume 1401.3(5) Å3, Z = 2. Complex 4 is triclinic, space group P1, unit cell dimensions a = 10.801(2) Å, b = 12.554(3) Å, c = 15.219(3) Å, α = 105.672(4) °, β = 103.048 °, γ = 104.594(4) °, volume 1824.8(7) Å3, Z = 2, calculated density 1.428 Mg m−3. Copyright © 2003 John Wiley & Sons, Ltd.
The analysis of volatile trace compounds in landfill gases, compost heaps and forest air
Authors: Maillefer Sarah , Lehr Corinne R. , Cullen William R.
Published: January 2003

Landfill gas, cryotrapped on a loop fashioned from a length of a capillary gas chromatography (GC) column, was examined for volatile organometallic compounds (VOMCs) and for volatile organic compounds (VOCs) by using GC–mass spectrometry (MS). A large number of organic components were present and many were identified, but the only VOMCs present in high enough concentrations to be detected were trimethylstibine and tetramethyltin. The use of inductively coupled plasma (ICP)‐MS as an element‐specific detector allowed the identification of a number of other organometallic species in the landfill gas, including trimethylarsine and trimethylbismuth, and, for the first time, butyltrimethyltin and dibutyldimethyltin. The presence of molybdenum hexacarbonyl was confirmed. Gas from a large‐scale compost heap and from compost incubated in the laboratory contained iodomethane but no common VOMCs (GC–ICP‐MS). Only VOCs were present in forest air (GC–MS). Copyright © 2003 John Wiley & Sons, Ltd.
Preparation, characterization and biological activities of novel ferrocenyl‐substituted azaheterocycle compounds
Authors: Fang Jian‐Xin , Jin Zhong , Li Zeng‐Ming , Liu Wei
Published: January 2003

α‐Haloacetylferrocene and α‐triazolylacetylferrocene have been prepared from acetylferrocene and they have proved to be useful building blocks for the synthesis of ferrocenyl propenone. Two new types of ferrocenyl vinyl triazole compound, (Z,E)‐ferrocenyl‐[1‐(1,2,4‐triazol‐1‐yl)‐2‐phenyl]‐vinyl‐ones, have been synthesized and their structures characterized by crystal X‐ray diffraction analysis. It has been shown for the first time that ferrocene, as an organometallic compound, has been introduced into bioactive triazole compounds in search of potent bioactive substances. Their biological activities are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Combating prejudice and racism: new interventions from a functional analysis of racist language
Authors: Guerin Bernard
Published: February 2003

Based on a conversational model of language‐use‐in‐social‐context, this article focuses on one particular form of racist and prejudiced talking that has not received enough attention—conversations in which racist statements function to maintain groups and relationships rather than seriously promote racism. Despite their casualness, such statements are still pernicious, and a range of potential interventions are proposed for this language function. These involve actively altering a community's discursive resources to include more rejoinders to racist comments. Such rejoinders must be utilized in the most appropriate way for any relationship, and this might mean polite corrections, witty repartee, strong put‐downs to silence someone making racist comments, or as counter‐jokes to racist jokes, depending upon the social context and power relations involved. Copyright © 2003 John Wiley & Sons, Ltd.
The prevention of depressive symptoms in rural Australian women
Authors: Day Chris , Kane Robert T. , Roberts Clare
Published: February 2003

Two interventions aimed at preventing depressive symptoms in women living in Western Australian rural communities were evaluated against a no‐intervention control condition. The standard intervention was based upon traditional cognitive‐behaviour treatments for depression; the experimental intervention was based upon prevention strategies derived from the learned helplessness model of depression (e.g. Peterson, Maier, & Seligman, 1993). Seventy‐six women were randomly assigned to either the standard or the experimental group, and a further 20 women formed a no‐intervention control group. The standard group showed a reduction in depressive symptoms at post‐test, but no effects at 6‐week or 6‐month follow‐ups. In contrast, a reduction in depressive symptoms did not appear for the experimental group until the 6‐week follow‐up at which time a less depressive attributional style was also evident; these effects were even more pronounced at the 6‐month follow‐up. The no‐intervention control group showed no changes across time. It is argued that these results support the applicability of prevention strategies based on the learned helplessness model to this population. Copyright © 2003 John Wiley & Sons, Ltd.
Expanding the traditional user versus non‐user dichotomy amongst ecstasy users
Authors: McMillan Brian , Sherlock Kellie , Conner Mark
Published: February 2003

Differences in the drug use characteristics and psychosocial variables in the use and non‐use of ecstasy within 845 16–25 year‐olds in the UK was examined. Based on levels of ecstasy use and intentions, two groups of non‐users (resistant and vulnerable), three groups of users (light, moderate and heavy) and an ex‐user group were identified. It was found that there is predictive utility in this way of expanding the widely employed ‘user versus non‐user’ dichotomy. Resistant non‐users were more likely to be younger, female, and were characterized by lower levels of use of four other drugs (amphetamine, cannabis, cocaine and LSD). Those ‘at risk’ of using ecstasy reported more frequent use of amphetamine, LSD, and cannabis than resistant non‐users. Heavy user groups reported using amphetamine, cocaine and LSD more frequently than all the other groups. Having ecstasy using friends increased the odds of being an ‘at risk’ non‐user or an ecstasy user. Normative influence also differentiated between the three user groups (light, moderate, and heavy). Beliefs about ecstasy use being immoral, ecstasy offers being difficult to resist, ecstasy use making one feel guilty and ecstasy being readily available differentiated between user and non‐user groups. These factors could usefully inform the content of health education materials designed to change ecstasy use. Copyright © 2003 John Wiley & Sons, Ltd.
Rhetorical representations of masculinities in South Africa: moving towards a material‐discursive understanding of men
Authors: Luyt Russell
Published: February 2003

A material‐discursive perspective holds advantage in understanding male realities. It seeks to integrate dominant approaches that appear anaemic in their failure to capture the interplay between the material and discursive realms of human existence. Three dominant metaphorical themes in the rhetorical representation of South African masculinities are described in an attempt to illustrate the complexity of embodied masculine experience. In this sense the discussion seeks to reveal the dynamic nature of masculine debate and lived experience across differing contexts. It serves to underline the importance of adopting a material‐discursive perspective in understanding men, which recognizes that they do not exist as a homogeneous social group, and as such experience their masculinities in a variable and changing fashion. The theoretical amalgamation of social representations and rhetoric is argued to provide a useful analytical tool in an endeavour of this nature. It is suggested that the rhetorical approach problematizes an overly consensual view of social reality that social representations theory typically promotes. Copyright © 2003 John Wiley & Sons, Ltd.
Phase II trial of cyclophosphamide, vincristine, and dexamethasone in the treatment of androgen‐independent prostate carcinoma
Authors: Daliani Danai D. , Assikis Vasily , Tu Shi‐Ming , Papandreou Christos N. , Pagliaro Lance C. , Holtkamp Tammy , Wang Xumei , Thall Peter F. , Logothetis Christopher J.
Published: February 2003

BACKGROUND

In this Phase II study, the authors assessed the toxicity and anti‐tumor activity of a combination of oral cyclophosphamide, oral low‐dose dexamethasone, and intravenous vincristine (CVD) in patients with metastatic androgen‐independent prostate carcinoma (AI‐PCa).

METHODS

Patients with histologic proof of adenocarcinoma of the prostate progressing despite adequate hormonal therapy and adequate organ function were treated with oral cyclophosphamide, 250 mg/daily (Days 1–14); intravenous vincristine, 1 mg daily (Days 1, 8, 15); and oral dexamethasone, 0.75 mg twice a day (Days 1–14) in 28‐day cycles. Study endpoints were toxicity, rate of prostate specific antigen (PSA) decline > 50%, and/or measurable disease response.

RESULTS

Fifty‐two (95%) of 55 registered patients were evaluable. The majority (65%) of patients had received prior chemotherapy. The median number of treatment cycles given was two (range, one–seven cycles). Twenty‐nine percent of the patients were found to have a > 50% decline in PSA level compared with baseline levels, and 25% of the patients with bidimensionally measurable soft‐tissue or visceral disease were found to have a partial response. The median progression‐free survival duration was 10 weeks, and the median overall survival duration was 10.6 months. There were no thromboembolic events, and hematologic and nonhematologic toxicity was minimal.

CONCLUSIONS

CVD was found to be an active and well‐tolerated regimen for AI‐PCa. The low toxicity profile makes CVD a useful treatment option for patients with significant comorbidities and high risk for treatment‐related toxicity, especially thromboembolic events and myelotoxicity. Cancer 2003;97:561–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11078
Low expression of p27 indicates a poor prognosis in patients with high‐grade astrocytomas
Authors: Kirla Ruut M. , Haapasalo Hannu K. , Kalimo Hannu , Salminen Eeva K.
Published: February 2003

BACKGROUND

Two families of tumor suppressor genes, Cip/Kip (p21, p27, and 57) and INK4 (p15, p16, p18, and p19), regulate cell proliferation and neoplastic transformation. p27 exerts its suppressor effect through cyclin E‐dependent kinase (CDK2) by inhibiting the phosphorylation of pRb by CDK2, which, in turn, arrests cells in the G1‐phase. p21 has a similar effect in addition to participating in the p53 dependent CDK4‐mediated and CDK6‐mediated pathway. The authors studied the prognostic significance of p21 and p27 in patients with high‐grade astrocytomas who were treated with radiotherapy.

METHODS

The expression of p27 and p21 was analyzed immunohistochemically in 52 glioblastomas and 25 anaplastic astrocytomas. All patients underwent surgery for the first time and were treated with adjuvant external radiotherapy.

RESULTS

The p27 labeling index (LI) was < 30% in 36% of tumors, 30–50% in 25% of tumors, and > 50% in 39% of tumors. A significant difference in cumulative survival was observed between these groups (P = 0.0072; log‐rank test). The p21 LI was < 30% in 48% of tumors, 30–50% in 39% of tumors, and > 50% in 13% of tumors; these groups did not differ significantly in survival. In multivariate Cox analysis, p27 LI was an independent prognostic factor (P = 0.0008). The grade of malignancy and proliferation activity also were independent prognostic factors.

CONCLUSIONS

Although p27 and p21 are parallel cell‐cycle regulators, only p27 has independent prognostic value in patients with malignant astrocytomas. It appears that decreased levels of p21/p27 are associated with a poor prognosis and short survival. Cancer 2001;97:644–8. © 2003 American Cancer Society.

DOI 10.1002/cncr.11079
Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma
Authors: Goffin John R. , Chappuis Pierre O. , Bégin Louis R. , Wong Nora , Brunet Jean‐Sébastien , Hamel Nancy , Paradis Ann‐Josée , Boyd Jeff , Foulkes William D.
Published: February 2003

BACKGROUND

Overexpression of p53 has been associated with poor survival following breast carcinoma. BRCA1 interacts biochemically with p53 and may also contribute to poor outcome when constitutionally mutated. The joint effect of both abnormalities has not been studied. The primary objective of this study was to assess the impact of germline BRCA1 mutations and p53 overexpression on survival after 10 years of follow‐up.

METHODS

A historical cohort of Ashkenazi Jewish women 65 years or younger with invasive breast carcinoma was tested for BRCA1 founder mutations. p53 overexpression was assessed by immunohistochemistry. Clinicopathologic information was obtained by chart review.

RESULTS

In total, 278 women were analyzed. On univariate analysis, p53 overexpression (n = 63) was prognostic for worse overall survival (relative risk [RR] 2.6, P = 0.001) whereas BRCA1 germline mutations (n = 30) were of borderline significance (RR 1.9, P = 0.052). In the lymph node‐negative subpopulation, BRCA1 mutation status conferred a higher mortality on univariate (RR 5.6, P < 0.001) and multivariate (RR 3.5, P = 0.03) analyses. There was a trend in favor of a worse prognosis for women who carried a germline BRCA1 mutation and whose tumor overexpressed p53. When compared with noncarriers, BRCA1 mutation carriers had a worse overall survival if they did not receive adjuvant chemotherapy (RR 3.3, P= 0.01) or adjuvant hormonal therapy (RR 2.3, P = 0.02).

CONCLUSIONS

Germline BRCA1 mutations and p53 overexpression carry a negative prognosis that is not additive to known prognostic factors. Given the experimental sensitivity of BRCA1‐mutated cells to chemotherapy, the worse survival among BRCA1 mutation‐carrying lymph node‐negative breast carcinoma patients may be partly explained by the significantly lower proportion of lymph node‐negative patients who received adjuvant chemotherapy (P < 0.001). Cancer 2003;97:527–36. © 2003 American Cancer Society.

DOI 10.1002/cncr.11080
A Phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma
Authors: Tiersten Amy D. , Nelsen Caron , Talbot Susan , Vahdat Linda , Fine Robert , Troxel Andrea , Brafman Lois , Shriberg Laureen , Antman Karen , Petrylak Daniel P.
Published: February 2003

BACKGROUND

The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P‐glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over‐express P‐glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC).

METHODS

Thirty‐six patients with MBC were treated with estramustine 900 mg/m2 per day divided into 3 doses given on Days 1–3 and docetaxel 70 mg/m2 given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC.

RESULTS

Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14–48%). The median progression free survival was 4 months (range, 1–41 months), and the median overall survival was 17 months (range, 2–45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy‐five percent of patients experienced either an improvement or no change in quality of life.

CONCLUSIONS

The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life. Cancer 2003;97:537–44. © 2003 American Cancer Society.

DOI 10.1002/cncr.11082
Survival of patients with metastatic breast carcinoma
Authors: Chang Jenny , Clark Gary M. , Allred D. Craig , Mohsin Syed , Chamness Gary , Elledge Richard M.
Published: February 2003

BACKGROUND

Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma.

METHODS

The prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S‐phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c‐erbB‐2, p53, and bcl‐2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs).

RESULTS

The median duration of survival was 17.8 months (95% confidence interval, 15.2–21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl‐2 expression, together with c‐erbB‐2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl‐2 expression were significant predictors of worse survival (P < 0.05).

CONCLUSIONS

In addition to traditional risk factors, bcl‐2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting. Cancer 2003;97:545–53. © 2003 American Cancer Society.

DOI 10.1002/cncr.11083
Radiofrequency ablation of adrenal tumors and adrenocortical carcinoma metastases
Authors: Wood Bradford J. , Abraham Jame , Hvizda Julia L. , Alexander H. Richard , Fojo Tito
Published: February 2003

BACKGROUND

The current study was performed to analyze the feasibility, safety, imaging appearance, and short‐term efficacy of image‐guided percutaneous radiofrequency ablation (RFA) of primary and metastatic adrenal neoplasms including adrenocortical carcinoma.

METHODS

The procedure was performed using 36 treatment spheres on 15 adrenocortical carcinoma primary or metastatic tumors in eight patients over 27 months. Tumors ranged from 15 to 90 mm in greatest dimension with a mean of 43 mm. All patients had unresectable tumors or were poor candidates for surgery. Mean follow‐up was 10.3 months.

RESULTS

All patients were discharged or were free of procedure‐related medical care 6–48 hours after the procedures without major complications. All treatments resulted in presumptive coagulation necrosis by imaging criteria, which manifested as loss of previous contrast enhancement in ablated tissue. Eight of 15 (53%) posttreatment thermal lesions lost enhancement and stopped growing on latest follow‐up computed tomographic scan. Three of 15 (20%) demonstrated interval growth and four did not change in size. Of these four lesions, two showed contrast enhancement. For smaller tumors with a mean greatest dimension less than or equal to 5 cm, 8 of 12 (67%) tumors were completely ablated, as defined by decreasing size and complete loss of contrast enhancement. Three of 15 (20 %) tumors and related thermal lesions were found to have disappeared nearly completely on imaging.

CONCLUSIONS

Percutaneous, image‐guided RFA is a safe and well tolerated procedure for the treatment of unresectable primary or metastatic adrenocortical carcinoma. The procedure is effective for the short‐term local control of small adrenal tumors, and is most effective for tumors less than 5 cm. The survival rate for patients with adrenocortical carcinoma improves when radical excision is performed in selected patients. Aggressive local disease control may potentially influence survival as well. However, further study is required to evaluate survival impact, document long‐term efficacy, and to determine if RFA can obviate repeated surgical intervention in specific clinical scenarios. Cancer 2003;97:554–60. Published 2003 by the American Cancer Society.

DOI 10.1002/cncr.11084
Health‐related quality of life of cancer and noncancer patients in Medicare managed care
Authors: Baker Frank , Haffer Samuel C. , Denniston Maxine
Published: February 2003

BACKGROUND

Data from the Health Care Financing Administration's (HCFA) Medicare Health Outcomes Survey (MHOS) of patients enrolled in managed care services through Medicare were analyzed. The MHOS provided baseline estimates of quality of life of cancer survivors in comparison to a frequency age‐matched cohort of noncancer patients.

METHOD

In 1998, the MHOS was mailed to a random sample of 279,135 beneficiaries. Completed surveys were received from 167,096 respondents (60%). Some 22,747 respondents who had been diagnosed with cancer were frequency age matched to an equal number of noncancer patients.

RESULTS

Cancer survivors had statistically significantly poorer scores than noncancer patients on all eight subscales as well as on the Physical Component and Mental Component summary measures of the Medical Outcomes Study Short Form‐36 (MOS SF‐36). Comparisons by type and number of cancers for which an individual was currently in treatment showed lowest quality of life for those in treatment for lung carcinoma, followed by those who were in treatment for more than one type of cancer.

CONCLUSION

The data suggest that cancer shows negative effects on health‐related quality of life that are not explainable by simple effects of age because frequency age‐matched cancer survivors had statistically significantly lower scores on all 10 scores of the MOS SF‐36. Effect sizes are evaluated to determine the clinical significance of these differences in health‐related quality of life. The MHOS offers useful data for planning and improving cancer policy and programs. Cancer 2003;97:674–81. Published 2003 by the American Cancer Society.

DOI 10.1002/cncr.11085
Prognostic factors in neuroendocrine small cell cervical carcinoma
Authors: Chan John K. , Loizzi Vera , Burger Robert A. , Rutgers Joanne , Monk Bradley J.
Published: February 2003

BACKGROUND

The purpose of this study was to evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine (NE) cervical carcinoma.

METHODS

All patients with NE cervical carcinoma diagnosed between 1979–2001 were identified from tumor registry databases at two hospitals. Data were collected from hospital charts, office records, and tumor registry files. The impact of clinical and pathologic risk factors on the survival of patients with small cell NE carcinoma of the cervix was evaluated using Kaplan–Meier life table analyses and log‐rank tests. The independent prognostic factors found to be predictive of survival in univariate analysis were evaluated using Cox regression. All tests were two‐tailed with P values < 0.05 considered significant.

RESULTS

Thirty‐four patients (median age, 42 years) were diagnosed with neuroendocrine cervical carcinoma, which included 21 with International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, 6 with FIGO Stage II disease, 5 with FIGO Stage III disease, and 2 with FIGO Stage IV disease. Seventeen patients underwent a radical and 6 patients underwent a simple hysterectomy. Fourteen women received adjuvant therapy with pelvic radiation and/or cisplatin‐based chemotherapy. Ten women received primary radiotherapy with (n = 5) or without (n = 4) chemotherapy and the remaining patient refused therapy. Women with early‐stage (Stage I‐IIA) disease had median survival rates of 31 months compared with 10 months in the advanced‐stage (Stage IIB‐IVB) group (P = 0.002). In univariate analysis, advanced stage (P = 0.002), tumor size >2 cm (P = 0.02), margin involvement (P = 0.016), pure versus a mixed histologic pattern (P = 0.04), margin status (P = 0.016), and smoking (P = 0.04) were considered poor prognostic factors. In multivariate analysis, smoking for early‐stage patients and stage of disease in the overall population remained as independent prognostic factors of survival.

CONCLUSIONS

Smoking and advanced stage are reported to be poor prognostic factors for survival in patients with NE small cell carcinoma of the cervix. Only those with early lesions amenable to extirpation are cured. The role of primary or postoperative radiation with or without chemotherapy is unclear and yields uniformly poor results, particularly in patients with advanced lesions. Clinical trials are needed. Cancer 2003;97:568–74. © 2003 American Cancer Society.

DOI 10.1002/cncr.11086
Protease‐activated receptor (PAR)‐1 and PAR‐2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomas
Authors: Jin Enjing , Fujiwara Masakazu , Pan Xin , Ghazizadeh Mohammad , Arai Satoru , Ohaki Yoshiharu , Kajiwara Keiko , Takemura Tamiko , Kawanami Oichi
Published: February 2003

BACKGROUND

Cell growth can be induced via elicitation of protease‐activated receptors (PAR) with serine proteases such as thrombin and trypsin.

METHODS

To understand whether PAR are involved in tumor vessel formation in the neoplastic cell‐bearing alveolar walls, immunohistochemical and reverse transcriptase‐polymerase chain reaction analyses were performed using the lung tissues from 16 patients with primary lung adenocarinomas.

RESULTS

In microdissected tumor alveolar walls, the expressions of PAR‐1 and PAR‐2 mRNA were increased by 10‐fold (P < 0.05) and 16‐fold (P < 0.01), respectively, as compared with normal alveolar walls. Confocal microscopy revealed that tumor capillary endothelial cells in alveolar walls lost thrombomodulin expression. Instead, the expression of PAR‐2 often became obvious at the normal border. Both PAR‐1 and PAR‐2 were expressed in the microvessel endothelial cells in tumors. Trypsin mRNA was expressed in 7 of the 16 cancer cell‐bearing tissue specimens in contrast to 1 of the 14 normal alveolar walls. Immunohistochemically, trypsin was positive in the neoplastic cells from 10 patients and in lung adenocarcinoma cell lines (A549, HLC‐1, LC‐2, and PC‐14). An in vitro assay showed a significant increase in idoxuridine (IdU) or bromodeoxyuridine uptake in human pulmonary artery endothelial cells and human umbilical cord vein endothelial cells after treatments with α‐thrombin or activating peptides; SFLLRN for PAR‐1 and SLIGKV for PAR‐2, respectively.

CONCLUSIONS

Thus, proliferation of alveolar capillary endothelial cells is initialized in part by PAR activation with serum thrombin and neoplastic cell‐released trypsin. These results suggest a synergistic effect of PAR with vascular endothelial growth factor in alveolar angiogenesis. Cancer 2003;97:703–13. © 2003 American Cancer Society.

DOI 10.1002/cncr.11087
Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia
Authors: Garcia‐Manero Guillermo , Jeha Sima , Daniel Jerry , Williamson Jason , Albitar Maher , Kantarjian Hagop M. , Issa Jean‐Pierre J.
Published: February 2003

BACKGROUND

Aberrant methylation of promoter‐associated cystosine‐guanine (CpG) islands is an epigenetic modification of DNA frequently observed in adult patients with acute lymphocytic leukemia (ALL). This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL.

METHODS

To investigate the methylation characteristics of pediatric patients with ALL and to determine whether DNA methylation can explain prognostic or biologic differences between pediatric and adult patients, the authors analyzed the methylation status of 7 promoter‐associated CpG islands in 16 pediatric patients with ALL and compared them with the methylation characteristics of a cohort of adult patients with ALL. The genes analyzed included the estrogen receptor gene (ER), multidrug resistance gene 1 (MDR1), p15, C‐ABL, CD10, p16, and p73.

RESULTS

The mean methylation densities of ER, MDR1, CD10, p15, and C‐ABL were 25.4%, 16.4%, 5.23%, 4.24%, and 4%, respectively. P16 was methylated in 11.7% of patients, and p73 was methylated in 17.6% of patients. One patient (6.2%) had methylation of 0 genes, 15 patients (93.7%) had methylation of ≥ 1 gene, and 4 patients (25%) had methylation of 3–4 genes. Methylation of all these genes was < 2% (or methylation specific polymerase chain reaction negative) in nonneoplastic tissues. A significant inverse correlation was observed between methylation of CD10 and CD10 expression. No differences were observed between the methylation characteristics of pediatric patients and adult patients.

CONCLUSIONS

The results indicate that DNA methylation is common in pediatric patients with ALL and that methylation of the genes studied does not account for prognostic differences between pediatric patients and adult patients with ALL. Cancer 2003;97:695–702. © 2003 American Cancer Society.

DOI 10.1002/cncr.11090
Detection of chromosomal aneusomy by fluorescence in situ hybridization for patients with nipple discharge
Authors: Yamamoto Daigo , Senzaki Hideto , Nakagawa Hiroyuki , Okugawa Homa , Gondo Hideki , Tanaka Kanji
Published: February 2003

BACKGROUND

Breast carcinoma and precancer are believed to start in the lining of the milk duct or lobule. Ductography and fiberoptic ductoscopy (FDS) are used to identify abnormal intraductal lesions, although it is difficult to distinguish malignant from benign cases. Therefore, we studied the clinical usefulness of fluorescence in situ hybridization (FISH) analysis of a numerical aberration of chromosomes (aneusomy) using ductal lavage from patients with nipple discharge.

METHODS

We applied ductography and FDS to 90 women who had nipple discharge. Ductal lavages obtained from patients with positive ductography and/or FDS findings were subjected to cytology and FISH analysis using centromere probes for chromosomes 1, 11, and 17. Patients with samples that showed aneusomy in at least one of the three chromosomes were diagnosed as positive.

RESULTS

Histologic evaluation revealed 54 benign lesions and six malignancies. The sensitivity, specificity, and diagnostic accuracy were 33.3%, 88.9%, and 83.3%, respectively, for cytology and 100%, 100%, and 100%, respectively, for FISH.

CONCLUSION

The results demonstrated that FISH has a diagnostic accuracy comparable to cytology. This technique has 100% specificity is making a definitive diagnosis of malignancy in patients with indeterminate cytologic results, suggesting that FISH diagnosis can be a good adjunct to cytology. Cancer 2003;97:690–4. © 2003 American Cancer Society.

DOI 10.1002/cncr.11091
Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors
Authors: Shimada Hideaki , Ochiai Takenori , Nomura Fumio
Published: February 2003

BACKGROUND

There have been very few large‐scale, multiinstitutional studies of surveillance of serum p53 antibodies (S‐p53 Abs) in patients with various malignant tumors.

METHODS

A highly specific, quantitative enzyme‐linked immunosorbent assay (ELISA) kit was developed and used to evaluate the efficiency of detecting p53 Abs. A cut‐off value was established by analyzing sera from 205 healthy volunteers as reference individuals. Sera from 1085 patients with various types of primary malignant tumors were studied for the presence of S‐p53 Abs before treatment. Sera from 34 patients were selected randomly for a competition assay to ensure that antibodies were specific to p53 protein. Carcinoembryonic antigen (CEA) was assessed to compare its positive rate with the positive rate of S‐p53 Abs.

RESULTS

The median value of S‐p53 Abs in healthy control individuals was 0.33 U/mL (range, 0.0–4.39 U/mL). Based on reference values that were calculated using parametric determination of the lower 0.95 fraction of the reference distribution in healthy control individuals, the cut‐off value was determined as 1.3 U/mL. Two hundred twenty‐one of 1085 patients (20.4%) were positive for S‐p53 Abs. The highest relevance of S‐53 Abs was associated with head and neck carcinoma (32%), followed by esophageal carcinoma (30%), colorectal carcinoma (24%), and carcinoma of the uterus (23%). The positive rate for S‐p53 Abs was higher compared with the positive rate for CEA in patients with squamous cell carcinoma.

CONCLUSIONS

Surveillance of S‐p53 Abs is useful in detecting various types of malignant tumors, particular in patients with squamous cell carcinoma. Cancer 2003;97:682–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11092
R‐Ras promotes tumor growth of cervical epithelial cells
Authors: Rincón‐Arano Héctor , Rosales Ricardo , Mora Nancy , Rodriguez‐Castañeda Armando , Rosales Carlos
Published: February 2003

BACKGROUND

R‐Ras is 55% identical to H‐Ras. However, these two oncogenes seem to have different tumor‐transforming potential. R‐Ras induced cell transformation in fibroblasts but not in other cell types. R‐Ras also reportedly induces a more invasive phenotype in breast epithelial cells through integrin activation. The authors studied the mechanisms whereby R‐Ras induces a malignant phenotype.

METHODS

Dominant negative (R‐Ras43N) and constitutively active (R‐Ras87L) mutants of R‐Ras were stably transfected into human cervical epithelium C33A cells. Transfected cells were analyzed for adhesion, cell spreading, migration, and growth in culture and in nude mice. The activity of extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase (PI 3‐K) also was determined by Western blot analysis and by in vitro kinase assays.

RESULTS

R‐Ras87L‐transfected cells, but not R‐Ras43 N‐transfected cells, had a higher growth rate in nude mice and in culture compared with control cells. None of the transfected C33A cells showed an increase in cell adhesion to fibronectin or collagen I, nor did they show an increment of β1 integrin affinity. However, cells that expressed R‐Ras87L, but not cells that expressed R‐Ras 43N, presented a marked increase in cell spreading and migration through collagen‐coated membranes. Increases in cell proliferation, spreading, and migration induced by R‐Ras87L were inhibited by the PI 3‐K inhibitor LY294002. In addition, PI 3‐K activity, but not ERK activity, was increased only in cells that expressed R‐Ras87L.

CONCLUSIONS

These data suggest that the oncogene R‐Ras promotes tumor growth of cervical epithelial cells and increases their migration potential over collagen through a pathway that involves PI 3‐K. Cancer 2003;97:575–85. © 2003 American Cancer Society.

DOI 10.1002/cncr.11093