bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine‐based regimens
Authors: Wierda William , O'Brien Susan , Faderl Stefan , Ferrajoli Alessandra , Wang Xuemei , Do Kim‐Anh , Garcia‐Manero Guillermo , Thomas Deborah , Cortes Jorge , Ravandi‐Kashani Farhad , Giles Francis , Lerner Susan , Kantarjian Hagop , Keating Michael
Published: December 2005

BACKGROUND

Combining therapeutics with single‐agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL.

METHODS

Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared.

RESULTS

Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, β‐2 microglobulin, and the number of prior treatments.

CONCLUSIONS

The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen. Cancer 2006. © 2005 American Cancer Society.
Efficacy of caspofungin against invasive Candida or invasive Aspergillus infections in neutropenic patients
Authors: Betts Robert , Glasmacher Axel , Maertens Johan , Maschmeyer Georg , Vazquez Jose A. , Teppler Hedy , Taylor Arlene , Lupinacci Robert , Sable Carole , Kartsonis Nicholas
Published: December 2005

BACKGROUND

Neutropenia is an indicator of poor prognosis in patients with fungal infections. All available clinical trial experience from the caspofungin development program was reviewed to ascertain the efficacy of caspofungin in neutropenic patients with documented invasive aspergillosis (IA) or invasive candidiasis (IC).

METHODS

The review was limited to neutropenic patients with proven IC or proven/probable IA at caspofungin onset. Data were available from four clinical trials. All patients had an absolute neutrophil count < 500/mm3 at the initiation of caspofungin. In all cases caspofungin was administered as monotherapy at a dose of 50 mg/day, after a 70‐mg loading dose. In all patients efficacy was assessed at the completion of caspofungin therapy. Success included complete and partial responses.

RESULTS

Sixty‐eight neutropenic patients were identified with documented invasive infection, including 27 with IC and 41 with IA. Most patients had acute or chronic leukemia. A favorable response was noted in 63% (17 of 27 patients) of patients with IC, including a 58% (14 of 24 patients) response as first‐line therapy and a 100% (3 of 3 patients) response as salvage therapy. Success in candidemia was 68% (17 of 25 patients). Outcomes across the different Candida species were similar. Favorable responses were noted in 39% (16 of 41 patients) of patients with IA, including a 42% (5 of 12 patients) response as first‐line therapy and 38% (11 of 29 patients) response as salvage therapy. Success by site of IA was 40% for pulmonary (12 of 30 patients), 43% for sinus (3 of 7 patients), and 25% for skin/disseminated site (1 of 4 patients).

CONCLUSIONS

A review of the caspofungin database demonstrates that this echinocandin is effective in neutropenic patients with documented cases of IC or IA. Cancer 2006. © 2005 American Cancer Society.
The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma
Authors: Sengupta Shomik , Lohse Christine M. , Cheville John C. , Leibovich Bradley C. , Thompson R. Houston , Webster W. Scott , Frank Igor , Zincke Horst , Blute Michael L. , Kwon Eugene D.
Published: December 2005

BACKGROUND

Prognostic nomograms are used increasingly in clinical trials and to guide surveillance for patients with renal cell carcinoma (RCC). An elevated erythrocyte sedimentation rate (ESR) reportedly has been associated with a poor prognosis among patients with RCC, but the ESR is not incorporated into existing nomograms. Hence, the current study was conducted to expand on prior observations pertaining to the ESR as a prognostic indicator in patients with RCC.

METHODS

The authors identified 3008 patients who underwent nephrectomy for RCC between 1970 and 2002. Disease‐specific survival was estimated using the Kaplan–Meier method, and its association with the ESR and other clinical and pathologic features was evaluated using Cox proportional hazards regression analysis.

RESULTS

A preoperative ESR was available for 1075 patients (35.7%), 501 of whom (46.6%) exhibited an elevated ESR, including 437 of 881 patients (49.2%) with clear cell RCC, 41 of 134 patients (30.6%) with papillary RCC, and 20 of 48 patients (41.7%) with chromophobe RCC. An elevated ESR was associated with adverse clinical, laboratory, and pathologic profiles for all three histologic subtypes. The risk ratios (RRs) and 95% confidence intervals (95% CIs) for death because of clear cell RCC, papillary RCC, and chromophobe RCC for patients with an elevated ESR were 3.6 (95% CI, 1.1–1.9), 3.8 (95% CI, 1.4–10.6), and 10.3 (95% CI, 1.2–89.5), respectively. The association between an elevated ESR and death from clear cell RCC persisted even after multivariate analysis (RR of 1.5; 95% CI, 1.2–2.0).

CONCLUSIONS

An elevated ESR in patients with RCC suggested the presence of aggressive disease and poorer outcomes after surgical treatment. For patients with clear cell RCC, the ESR provided useful information above and beyond traditional prognostic algorithms, and it may be valuable for preoperative prognostication. Cancer 2006. © 2005 American Cancer Society.
Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa
Authors: Holt Peter R. , Bresalier Robert S. , Ma Chan K. , Liu Kai‐Feng , Lipkin Martin , Byrd James C. , Yang Kan
Published: December 2005

BACKGROUND

Calcium and vitamin D are chemopreventive agents for colorectal neoplasia. Studies of the effects of calcium and vitamin D on early surrogate markers of reduced risk, such as proliferation, have been limited to evaluation of the flat colorectal mucosa. Biologic changes that may occur in colorectal adenomas after chemopreventive regimens have not been reported.

METHODS

In the current study, adenomatous polyps were transected, approximately 50% were removed for histologic examination, and the remnants tattooed before the administration of either calcium carbonate (1500 mg 3 times daily) plus vitamin D3 400 IU or a placebo for 6 months. At study end, polyp remnants were resected completely and were used for histologic examination. Immunohistochemical staining was performed in both flat mucosa and in polyp tissue. Proliferation was assessed by MIB‐1 staining; apoptosis was assessed by terminal deoxyuridine triphosphate‐biotin nick‐end labeling, BAK, and Bcl‐2 staining; and cytokeratin AE1, vitamin D receptor, MUC5AC mucin, and galectin‐3 were assessed by immunohistochemisty.

RESULTS

Nineteen patients, including 11 patients in the treatment group and 8 patients in the control group, completed the study. Proliferative indices fell both in flat mucosa and in polyps in the treatment group, and there were no significant changes in the control group. Apoptosis and Bcl‐2 immunostaining were unchanged in both groups, but the frequency of BAK‐immunostained cells in the interior of polyps rose significantly. Vitamin D receptor staining increased slightly and significantly in flat rectal tissue in the treatment group. There were no significant changes in galectin‐3 staining, but a striking reduction in MUC5AC mucin staining in polyps was observed after treatment with calcium plus vitamin D.

CONCLUSIONS

The administration of a calcium plus vitamin D chemopreventive regimen resulted in several changes in adenomatous tissue that may have contributed to reduced polyp formation. Cancer 2006. © 2005 American Cancer Society.
Metaanalysis of the correlation between radiographic tumor response and patient‐reported outcomes
Authors: Victorson David , Soni Mehul , Cella David
Published: December 2005

BACKGROUND

The primary aim of the current study was to determine whether radiographic tumor response is associated with patient‐reported outcomes such as symptom response or health‐related quality of life.

METHODS

A metaanalysis was conducted of 21 available studies from 1995–2003 that provided data sufficient for examining the association between tumor response and patient‐reported outcomes, including symptom response and health‐related quality of life. A second aim was to examine the influence of possible moderating study variables on effect size variation.

RESULTS

As hypothesized, patient‐reported outcome improvement rates were most frequently associated with patients classified as a complete or partial response (CR/PR), followed by those with stable disease (SD) and progressive disease (PD). Moderate effect sizes were observed between the CR/PR and SD (effect size of 0.35) and CR/PR and PD categories (effect size of 0.43). A weak effect size was found between SD and PD (effect size of 0.16), raising concern over the meaningfulness of the SD category. No significant correlations were found between effect size and patient or study characteristics. Significant associations existed between treatment duration and age, study duration, survival, and symptom response rates, especially among PD patients.

CONCLUSION

Despite significant study‐to‐study heterogeneity, an important association exists in the correlation between tumor response and formal measures of change in patient‐reported outcomes. A better understanding of this relation would be enhanced if future reports included estimates of effect size in patient‐reported outcome change by tumor response category. Practical implications, limitations, and directions for future research are provided. Cancer 2006. © 2005 American Cancer Society.
Expression of the Bax inhibitor‐1 gene in pulmonary adenocarcinoma
Authors: Tanaka Ryota , Ishiyama Tadashi , Uchihara Teruhito , Inadome Yukinori , Iijima Tatsuo , Morishita Yukio , Kano Junko , Goya Tomoyuki , Noguchi Masayuki
Published: December 2005

BACKGROUND

The regulation of programmed cell death, or apoptosis, is crucial for normal development and for the maintenance of homeostasis. It has been shown that the novel antiapoptotic protein Bax inhibitor‐1 (BI‐1) represents a new type of regulator of cell death pathways controlled by Bcl‐2 and Bax.

METHODS

Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI‐1 gene expression was examined and compared with expression of the p53, bcl‐2 and Bax genes.

RESULTS

Fourteen of 32 tumors (43.8%) were positive for BI‐1 gene expression by in situ hybridization. BI‐1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading. Patients who had BI‐1‐positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI‐1‐negative adenocarcinoma. Eleven of 32 tumors (34.4%) were positive for the p53 protein, only 1 of 32 tumors (3.1%) was positive for the Bcl‐2 protein, and 26 of 32 tumors (81.3%) were positive for the Bax protein. Protein expressions of p53, Bcl‐2, and Bax, as detected by immunohistochemistry, were not associated with BI‐1 gene expression.

CONCLUSIONS

BI‐1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral‐type adenocarcinoma. It is believed that BI‐1 gene expression is conserved evolutionarily and may act as a key regulator of the apoptotic pathway in BAC. Cancer 2006. © 2005 American Cancer Society.
Optimal shape design for blade's surface of an impeller via the Navier–Stokes equations
Authors: Li Kaitai , Su Jian , Gao Limin
Published: December 2005

In this paper, a new principle of geometric design for blade's surface of an impeller is established. This is a thorough mathematical investigation of a shape control problem for the optimal design of an impeller's blade while 3D rotating Navier–Stokes equations are as the state equations in the control problem. The objective is to design the blade such that the viscous drag is minimized. Establishing a new curvilinear coordinate system, we depart from a standard domain transformation commonly used in the engineering literature and utilizing it we rephrase the design problem in one on a fixed domain. Certain advantages of our approach as no need for mesh regeneration and node redistribution and 3D mesh quality improvement are evident. Furthermore, in new coordinate system, it is easy to obtain gradient of optimal functional with respect to the surface of blade and to derive Euler–Lagrange equations for optimal solution which is an elliptic boundary value problem of fourth order. Moreover, we give the conjugate gradient algorithm for the control problem. Copyright © 2005 John Wiley & Sons, Ltd.
What makes workflows work in an opportunistic environment?
Authors: Deelman Ewa , Kosar Tevfik , Kesselman Carl , Livny Miron
Published: December 2005

In this paper, we examine the issues of workflow mapping and execution in opportunistic environments such as the Grid. As applications become ever more complex, the process of choosing the appropriate resources and successfully executing the application components becomes ever more difficult. This may include extension or reduction of the initial workflow mapping as necessary for the actual execution. In this paper, we focus on the interplay between a workflow‐mapping component that plans the high‐level resource assignments and the workflow executor that oversees the component execution. We concentrate particularly on issues of data management and we draw from the experiences with mapping and execution systems: Pegasus, DAGMan and Stork. Copyright © 2005 John Wiley & Sons, Ltd.
Implementing BPEL4WS: the architecture of a BPEL4WS implementation
Authors: Curbera Francisco , Khalaf Rania , Nagy William A. , Weerawarana Sanjiva
Published: December 2005

BPEL4WS (BPEL in short) is a business process definition language built natively on top of the Web services application model. BPEL provides a workflow‐oriented composition model for Web services applications, and is thus a central piece in the heavily componentized service‐oriented computing model. BPEL results from the merger of two distinct process metamodels (the process algebra model of XLANG and the graph‐oriented model of WSFL) into a coherent and powerful framework. Implementing BPEL thus presents significant challenges to middleware developers. This paper discusses those challenges and describes the design and architecture of the BPWS4J runtime, and a full implementation of the BPELWS 1.1 specification. Copyright © 2005 John Wiley & Sons, Ltd.
ScyFlow: an environment for the visual specification and execution of scientific workflows
Authors: McCann Karen M. , Yarrow Maurice , DeVivo Adrian , Mehrotra Piyush
Published: December 2005

With the advent of Grid technologies, scientists and engineers are building more complex applications to utilize distributed Grid resources. Core Grid services provide a path for accessing and utilizing these resources in a secure and seamless fashion. However, what the scientists need is an environment that will allow them to specify their application runs at a high organizational level, and then will support efficient execution across any given set or sets of distributed resources. We have been designing and implementing ScyFlow, a dual‐interface architecture, both Graphical User Interface (GUI) and Application Programming Interface (API), that addresses this problem. The scientist/user specifies the application tasks along with the necessary control and data flow, and then monitors and manages the execution of the resulting workflow across the distributed resources. In this paper, we utilize two scenarios to provide the details of the two modules of the project, the visual editor and the runtime workflow engine. Published in 2005 by John Wiley & Sons, Ltd.
A Prime Example of Hard‐Hard and Soft‐Soft Interactions: Complexes between 4,7‐Dioxa‐1,10‐diazabicyclo[8.6.6]docosa‐13,19‐diyne and Li+, Na+, Cu+, Ag+, Cd2+, Hg2+
Authors: Kunze Andreas , Gleiter Rolf , Rominger Frank
Published: December 2005

The crystal structures of 4,7‐dioxa‐1,10‐diazabicyclo[8.6.6]docosa‐13,19‐diyne (7), its N,N′‐dioxide derivative 10 and the complexes of 7 with LiClO4, NaNO3, CuI and AgI triflate, Cd(NO3)2, and HgCl2 were investigated. The Li+ and Na+ ions reveal a strong interaction between the ether bridge and the nitrogen atoms of 7. The CuI ion prefers an interaction between the nitrogen centers and the alkyne units whereas the AgI ion interacts with the hard oxygen and nitrogen centers as well as with the alkyne units. The reaction of HgCl2 with 7 in the presence of water afforded a molecule which could be looked at as the intermediate of a mercury‐catalyzed addition of water to the triple bonds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Hydride Transfer Reactivity of Mo(L)(H)(depe)2 (L = N, NBEt3)
Authors: Cugny Johan , Schmalle Helmut W. , Fox Thomas , Blacque Olivier , Alfonso Montserrat , Berke Heinz
Published: December 2005

Starting from Mo(N2)2(depe)2 (1), the nitrido complex Mo(N)(N3)(depe)2 (2) was obtained by the reaction of 1 with Me3SiN3. Subsequent reaction of 2 with HCl in CH3OH afforded the cationic imido chloride 3, which could be converted into the nitrido chloride 4 with sodium bis(trimethylsilyl)amide. From 3 and 4 the hydrido complexes of the type Mo(H)(L)(depe)2 [L = N (7), NBEt3 (8)] were obtained by the reaction with the hydride reagents LiBH4 and NaHBEt3. The hydridic character of the LnM–H bond of 8 was determined by DQCC measurements (bond ionicity i = 81 %). Hydride reactivity studies were carried out on 7 and 8; however, only 8 underwent hydride transfer reactions. 8 reacted with 4,4′‐dichlorobenzophenone and acetophenone to afford the corresponding alkoxide complexes Mo(NBEt3)(OCHRR′)(depe)2 [R, R′ = C6H4Cl (10); R = Me, R′ = Ph (11)]. The high propensity of 8 to undergo carbonyl insertion was documented further by reactions with CO2 and carbonylmetal compounds. Conversion with CO2 led to formation of the formato complex Mo(NBEt3)(OCHO)(depe)2 (9) and reactions with Fe(CO)5 and Re2(CO)10 resulted in the formation of Mo[(μ‐OCH)Fe(CO)4](NBEt3)(depe)2 (12) and Mo[(μ‐OCH)Re2(CO)9](NBEt3)(depe)2 (13). X‐ray diffraction studies were carried out on 1–4, 6, 8–10 and 12–14. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
The First Coordination Polymers Based on Octahedral Hexahydroxo Rhenium Cluster Complexes [Re6Q8(OH)6]4– (Q = S, Se) and Alkaline Earth Metal Cations
Authors: Mironov Yuri V. , Fedorov Vladimir E. , Bang Hyunjin , Kim Sung‐Jin
Published: December 2005

Seven novel octahedral cluster compounds [{Mg(H2O)5}2Re6S8(OH)6]·6H2O (1), [{Ca(H2O)3}2Re6S8(OH)6] (2), [{Ca(H2O)3}2Re6Se8(OH)6] (3), [{Sr2(H2O)10}Re6S8(OH)6]·6H2O (4), [{Sr2(H2O)10}Re6Se8(OH)6]·6H2O (5), [{Ba2(H2O)8}Re6S8(OH)6] (6), and [{Ba2(H2O)8}Re6Se8(OH)6] (7) were prepared by the direct reaction of K4[Re6S8(OH)6]·8H2O and K4[Re6Se8(OH)6]·8H2O with the cations of the elements of main group II. All compounds have been characterized by single crystal X‐ray diffraction. Compound 1 has a discrete molecular structure, compounds 4 and 5 have a one‐dimensional chain structure, and compounds 2, 3, 6, and 7 crystallize in two different types of two‐dimensional layered structure. This sulfur containing series has been characterized by luminescent spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Platinum‐Group Chelate Complexes with 9‐Hydroxyphenalenone Derivatives: Synthesis, Structures, Spectroscopic Properties and Cytotoxic Activities
Authors: Mochida Tomoyuki , Torigoe Reiko , Koinuma Takeo , Asano Chika , Satou Tadaaki , Koike Kazuo , Nikaido Tamotsu
Published: December 2005

The following platinum‐group chelate complexes with 5‐R‐9‐hydroxyphenalenone (L1: R = H; L2: R = Me; L3: R = Pr) have been prepared: [RhI(L)(CO)2] (1a: L = L1; 1b: L = L2; 1c: L = L3), [PdII(L)2] (2a: L = L2; 2b: L = L3), [PtII(L1)(NH3)2](NO3) (3), and (Bu4N)[PtII(L1)(Cl)2] (4). Compounds 1a and 1b are different colors in the solid state: yellow and deep red, respectively. X‐ray analysis revealed that 1a has a regular π–π stacking structure while 1b has a dimer‐like arrangement with a RhI–RhI distance of 3.2336(6) Å. Both solids were luminescent at 77 K. Compounds 2a and 2b are planar extended π‐conjugated complexes, which exhibit two‐dimensional stacking modes in the crystal. The solid‐state structure of complex 3 is hydrogen‐bonded in a polar arrangement. The cytotoxic activities of 1a, 3, and 4, evaluated in vitro against HL60 human acute myeloid leukemia cell lines, were comparable to that of cisplatin. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Heterobimetallic Ruthenium‐Cobalt Complexes Containing the Pentamethylcyclopentadienyl or Indenyl Ligand
Authors: Ng Sin Yee , Goh Lai Yoong , Koh Lip Lin , Leong Weng Kee , Tan Geok Kheng , Ye Suming , Zhu Yinghuai
Published: December 2005

The salt elimination reaction between NaCo(CO)4 and the ruthenium complexes LRu(diphos)Cl and [(Ind)Ru(CO)2Cl] afforded the Ru–Co bimetallic complexes [LRu(μ‐CO)2(μ‐diphos)Co(CO)2] [L = C5Me5 (Cp*), diphos = Ph2P(CH2)nPPh2, 3a: n = 1 , or 3b: n = 2; 3: L = C9H7 (Ind), diphos = Ph2PCH2PPh2 ] and [(Ind)Ru(CO)2Co(CO)4] (3d), respectively, in high yields. However, the same reaction with the monophosphane analogue, [(Ind)Ru(PPh3)2Cl], gave the heterobimetallic complex [(Ind)Ru(PPh3)(CO)(μ‐CO)Co(CO)3] (3e) in fair yield, together with redox‐initiated derivatives Ru(PPh3)2(CO)3 (4e) and [(Ind)Co(CO)(PPh3)] (6e). A similar redox process in the reaction of the dppf analogue, [(Ind)Ru(dppf)Cl] (dppf = 1,1′‐diphenylphosphanylferrocene) gave [Ru(dppf)(CO)3] (4f) and [(Ind)Co(CO)2] (6f), together with a complex salt [(Ind)Ru(dppf)(CO)][Co(CO4)] [5f·Co(CO)4]. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A Hetero Diels–Alder Concerted vs. Aldol Stepwise Mechanism in the Cyclization of Silyloxyazadienes with Aldehydes: A Theoretical Study
Authors: Bongini Alessandro , Panunzio Mauro
Published: December 2005

The Diels–Alder reaction of 3‐silyloxy‐2‐azadiene with formaldehyde has been studied at the B3LYP/6‐31G* level of theory and the role played by a Lewis acid evaluated. It is shown that the reaction is preferred when the Lewis acid coordinates to the aldehyde oxygen. This coordination allows for a concerted as well as a stepwise mechanism for the cyclization. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis of Spiro Carba‐Sugars by Ring‐Closing Metathesis
Authors: González‐Bello Concepción , Castedo Luis , Cañada Francisco Javier
Published: December 2005

Six conformationally restricted carba‐sugars have been synthesized by ring‐closing metathesis of a readily available diallyl keto derivative of (–)‐quinic acid. The rich functionality of the resulting spiro ketone was exploited for the diastereoselective synthesis of various spiro carba‐sugars: four of them polyhydroxylated and two aminopolyhydroxylated. The results of the testing of these compounds against various commercially available glycosidases (amyloglicosidase, α‐ and β‐galactosidase, α‐ and β‐ glucosidase, α‐mannosidase, trehalase and neuraminidase) are provided. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Neuroblastoma cell death in response to docosahexaenoic acid: Sensitization to chemotherapy and arsenic‐induced oxidative stress
Authors: Lindskog Magnus , Gleissman Helena , Ponthan Frida , Castro Juan , Kogner Per , Johnsen John Inge
Published: December 2005

Docosahexaenoic acid (DHA) is an ω‐3 polyunsaturated fatty acid vital for the developing nervous system and significantly decreased in neuroblastoma cells compared to nontransformed nervous tissue. We investigated whether supplementation of DHA affects the susceptibility of neuroblastoma cells to oxidative stress generated endogenously and in response to cytotoxic therapy. DHA, but not the monounsaturated oleic acid (OA), induced dose‐ and time‐dependent neuroblastoma cell death. DHA supplementation was associated with depolarization of the mitochondrial membrane potential, production of reactive oxygen species (ROS) and accumulation of DNA in sub‐G1 phase of the cell cycle. The antioxidant, vitamin E, inhibited mitochondrial depolarization and subsequent cell death induced by DHA, whereas, the mitochondrial pore inhibitor, cyclosporin A, partly inhibited DHA‐induced neuroblastoma cell death. Depletion of glutathione by L‐buthionine‐sulfoximine significantly enhanced the cytotoxic effects of DHA. Nontransformed fibroblasts were not substantially affected by DHA. DHA, but not OA, significantly enhanced the cytotoxicity of cisplatin, doxorubicin and irinotecan both in chemosensitive and in multidrug‐resistant neuroblastoma cells. DHA potently sensitized neuroblastoma cells to a clinically relevant concentration (1 μM) of arsenic trioxide (As2O3) and enhanced the effect of the nonsteroidal antiinflammatory drug (NSAID), diclofenac. These findings provide experimental evidence that the ω‐3 fatty acid, DHA, is cytotoxic to drug‐resistant neuroblastoma. The potent action of DHA with arsenic trioxide, NSAID and chemotherapeutic agents suggests clinical testing of this therapeutic concept in children with neuroblastoma. © 2005 Wiley‐Liss, Inc.
Body size and composition and the risk of gastric and oesophageal adenocarcinoma
Authors: MacInnis Robert J. , English Dallas R. , Hopper John L. , Giles Graham G.
Published: December 2005

Although evidence has been mounting that obesity may be related to the increased incidence of oesophageal and gastric cardia malignancies, these reports (mainly case‐control studies) have relied on imperfect measures of obesity such as body mass index (BMI), and generally have not clearly distinguished between anatomical subsites within the oesophagus and stomach. In a prospective study of people aged 27–75 years, we directly measured fat mass and fat‐free mass (using bioelectrical impedance analysis), height, weight and waist and hip circumferences. Among 41,295 people followed on average for 11.3 years, 30 cases with cancers in the gastric cardia or lower third of the oesophagus and 68 cases with noncardia gastric adenocarcinomas were ascertained via the population cancer registry. The risk of adenocarcinoma of the lower oesophagus and gastric cardia was positively associated with BMI with a hazards ratio (HR) and (95% confidence interval) for people with BMI ≥ 30 kg/m2 compared with those <25 kg/m2, of 3.7 (1.1–12.4), an HR per 10 cm increase in waist circumference of 1.46 (1.05–2.04), and a HR per 10 kg increase on fat‐free mass of 2.06 (1.15–3.69). Noncardia gastric adenocarcinoma showed little relationship with body size. We observed an increased risk of adenocarcinoma of the lower oesophagus and gastric cardia associated with increased BMI, central adiposity and the nonfat component of weight, but found no association with noncardia gastric adenocarcinoma. An increasing prevalence of obesity may be associated with the increasing incidence of gastro‐oesophageal cancer observed in many populations. © 2005 Wiley‐Liss, Inc.
Definition of an HPV18/45 cross‐reactive human T‐cell epitope after DNA immunisation of HLA‐A2/KB transgenic mice
Authors: McCarthy Corinna , Youde Sarah J. , Man Stephen
Published: December 2005

Although human papillomavirus (HPV) types 16 and 18 are the most common types associated with cervical cancer worldwide, other related HPV types such as HPV 35, 45 and 58 have significant prevalence in geographically distinct populations. For development of global prophylactic and therapeutic vaccine strategies, it is important to study immune responses against these viruses and to define the degree of cross‐reactivity between related HPV types. To investigate the potential for T cell cross‐reactivity after vaccination, HLA‐A2/Kb transgenic mice were immunised with DNA plasmid constructs containing HPV18 and 45 E6 and E7. Splenocytes from immunised mice were tested in direct ELIspot assays against overlapping pools of HPV 18 peptides. Immunisation with either HPV18 or HPV45 E6 DNA produced dominant T cell responses against an epitope (KCIDFYSRI) that was shared between HPV18 and HPV45. This peptide was shown to bind to HLA‐A*0201 but not Db or Kb molecules on the cell surface. Furthermore this peptide was shown to be immunogenic in vitro to human T cells from 2 out of 3 HLA‐A2+ healthy donors. Collectively, these results demonstrate that HPV 18 and 45 E6 DNA vaccines are immunogenic in mice and demonstrate that cross‐reactive T cell responses against closely related HPV types can be induced in vivo. The use of the HLA‐A2/Kb transgenic mice allowed definition of an HLA‐A*0201 binding peptide epitope that would have been rejected on the basis of predicted major histocompatibility complex binding affinity. © 2005 Wiley‐Liss, Inc.
Comparative genomic hybridization analysis on male breast cancer
Authors: Rudlowski Christian , Schulten Hans‐Jürgen , Golas Mariola Monika , Sander Bjoern , Barwing Roland , Palandt Jens‐Ekkehard , Schlehe Bettina , Lindenfelser Rüdiger , Moll Roland , Liersch Torsten , Schumpelick Volker , Gunawan Bastian , Füzesi László
Published: December 2005

The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for +8q and −16q with larger tumor size and −16q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including +1q, −8p, +8q, −13q, +16p, −16q, +17q and +20q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer. © 2005 Wiley‐Liss, Inc.
Age of diagnosis of colorectal cancer in HNPCC patients is more complex than that predicted by R72P polymorphism in TP53
Authors: Talseth Bente A. , Meldrum Cliff , Suchy Janina , Kurzawski Grzegroz , Lubinski Jan , Scott Rodney J.
Published: December 2005

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited cancer syndrome associated with germline mutations in DNA mismatch repair (MMR) genes. Recently a polymorphism at codon 72 (R72P) in the tumour suppressor gene TP53 has been implicated in the age of disease onset in HNPCC. In this report we have studied a large cohort of HNPCC patients to assess the impact of this polymorphism on disease expression and age of diagnosis of colorectal cancer (CRC). DNA samples from 218 HNPCC mutation positive patients from Australia and Poland were genotyped for the arginine to proline change at codon 72 in the TP53 gene. The association between the polymorphism and disease characteristics (mutation status, disease expression and age of diagnosis of CRC) was tested using Pearson's Chi‐square and Kaplan–Meier survival analysis. Our study of Australian and Polish HNPCC patients does not provide evidence for an association between the Arg/Pro (GC) genotype of the R72P polymorphism and age of diagnosis of CRC. The R72P polymorphism was examined in HNPCC patients and found to be not associated with disease development in either the Australian or Polish populations. When gene mutation status (hMLH1 or hMSH2) was included in the analysis some evidence of an affect was observed. The genotyping revealed in the Australian population that the R72P polymorphism was under‐represented in the hMSH2 group whereas it was over‐represented in the Polish hMSH2 group. A similar trend was observed for hMLH1 in both groups but was not significant. Age of diagnosis of CRC in HNPCC patients is therefore more complex than that predicted by the R72P TP53 polymorphism alone, suggesting an inter‐relationship with other genetic and/or environmental factors. © 2005 Wiley‐Liss, Inc.
Association of the ARLTS1 Cys148Arg variant with familial breast cancer risk
Authors: Frank Bernd , Hemminki Kari , Meindl Alfons , Wappenschmidt Barbara , Klaes Rüdiger , Schmutzler Rita K. , Untch Michael , Bugert Peter , Bartram Claus R. , Burwinkel Barbara
Published: December 2005

Recently, ARLTS1 (ADP‐ribosylation factor‐like tumor suppressor gene 1) has been identified as a tumor suppressor gene, playing a major role in apoptotic signaling. The ARLTS1 Trp149Stop mutation has been shown to predispose to general familial cancer and high‐risk familial breast cancer (BC), provoking the attenuation of apoptotic function. We studied the impact of the ARLTS1 Pro131Leu and Cys148Arg variants on high‐risk familial and familial BC risk, investigating 482 familial BC cases (including 305 high‐risk cases) and 530 control individuals. Unlike ARLTS1 Pro131Leu, Cys148Arg revealed a significant association with an increased risk of high‐risk familial BC (odds ratio (OR) = 1.47, 95% confidence interval (95% CI) = 1.04–2.06, p = 0.03) in a dose‐dependent manner (ptrend = 0.007). The genotype distribution of Cys148Arg in familial cases was similar, indicating significance as well (OR = 1.48, 95% CI = 1.10–1.99, p = 0.009; ptrend = 0.003). On the basis of the small number of 46 cases, we additionally showed an association between the Trp149Stop mutation and an increased risk of bilateral BC (OR = 4.11, 95% CI = 1.27–13.31, p = 0.011). © 2005 Wiley‐Liss, Inc.
Environmental life cycle assessment of a pre‐fragmented high explosive grenade
Authors: Hochschorner Elisabeth , Hägvall Joakim , Finnveden Göran , Griffing Evan , Overcash Michael
Published: December 2005

Organisations today face increasing environmental constraints, e.g. in the form of legal and customer requirements; the defence sector is no exception. There is a need to evaluate and limit environmental effects of defence activities and materiel. In this study we used quantitative Life Cycle Assessment (LCA) and a method for simplified LCA (the Material, Energy, Chemicals and Others (MECO) method) to assess the environmental impacts of a grenade. The aims of the study are to identify aspects in the grenade's life‐cycle that have the largest environmental impact, suggest improvement possibilities, make a comparison between different approaches for waste management of munitions, and to perform a demonstrative case for the application of LCA to munitions. Significant environmental aspects of the grenade's life‐cycle include use of metals, use of fossil fuels, and detonation outdoors. The study shows that an LCA can be used to analyse environmental impacts from munitions. The simplified LCA gave information that is complementary to the quantitative LCA. Copyright © 2005 Society of Chemical Industry
Power Doppler assessment of overall disease activity in patients with rheumatoid arthritis
Authors: Kiris Adem , Ozgocmen Salih , Kocakoc Ercan , Ardicoglu Ozge
Published: December 2005

Purpose.

To examine synovial vascularity and flow patterns in hand and wrist joints—metacarpophalangeal (MCP) joints and ulnar stiloid (USTL) regions—of patients with rheumatoid arthritis (RA) using power Doppler sonography (PDUS) and spectral Doppler analysis and to assess the accuracy of PDUS in detecting overall disease activity in RA patients.

Methods

Two hundred forty MCP joints and 48 USTL regions in 24 RA patients were examined. Patients were categorized into 2 groups—active and inactive—according to the American College of Rheumatology remission criteria. Resistance indexes (RIs) were measured.

Results

Flow signals were detected in 50 MCP joints (in 13 patients) and 24 USTL regions (in 16 patients) and spectral analysis was performed in 46 MCP joints (12 patients) and 23 USTL regions (16 patients). The sensitivity and specificity of PDUS in detecting disease activity in RA were 92% and 40%, respectively. There was a negative correlation between flow signal number and RI, with higher scores of flow signals corresponding to lower RIs.

Conclusion

PDUS appears to be a reliable method for assessing inflammatory activity in rheumatoid synovium. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:5–11, 2006
Incidence and clinical significance of spontaneous intrahepatic portosystemic venous shunts detected by sonography in adults without potential cause
Authors: Lin Zu‐Yau , Chen Shinn‐Cherng , Hsieh Ming‐Yen , Wang Chu‐Wen , Chuang Wan‐Long , Wang Liang‐Yen
Published: December 2005

Purpose

B‐mode and color Doppler sonography were used to assess the incidence and clinical significance of spontaneous intrahepatic portosystemic venous shunt in adults without detectable cause.

Methods

A total of 25,579 adults without potential cause of intrahepatic portosystemic venous shunt were screened using B‐mode sonography. Suspicion of shunt was confirmed by color Doppler sonography. Patients with shunt were followed up with sonography at 6‐ to 12‐month intervals and received dietary education to prevent the ingestion of extra‐large amounts of protein. During each sonography session, the patients were asked to report any experience of consciousness disturbance.

Results

Six patients (0.0235%) showed evidence of shunt on color Doppler sonography. Direct communication between a right portal branch and the inferior vena cava was found in 3 patients; a small aneurysm connecting a peripheral portal branch to the hepatic vein was found in the remaining 3 patients. Five patients were followed up (range, 12–60 months) and showed no change in the size of the shunt. None of the patients with shunt reported an experience of consciousness disturbance.

Conclusions

The incidence of spontaneous intrahepatic portosystemic venous shunt is extremely low in asymptomatic adult patients. Follow‐up and dietary control seen to be suitable for their management. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:22–26, 2006
The influence of athletic activity on the plantar fascia in healthy young adults
Authors: Uzel Murat , Cetinus Ercan , Ekerbicer H. Cetin , Karaoguz Ahmet
Published: December 2005

Purpose

Complaints deriving from the plantar fascia are relatively common in athletes. This study aimed to investigate the changes of thickness of plantar fascia via sonography in healthy young adults with different levels of activity.

Patients and Methods

One hundred ten adults with normal body mass index were separated into three groups according to activity level: sedentary (group 1, n = 50), athletic activity less than 7 hours per week (group 2, n = 30), and athletic activity 7 or more hours per week (group 3, n = 30). The thicknesses of the plantar fascia at origin and at a point 5 mm distal to origin were measured via sonography.

Results

The mean values of the thickness of the proximal plantar fascia (PFp) and the distal plantar fascia (PFd) in group 1 were similar to those of groups 2 and 3 (p > 0.05). The mean values of PFp and PFd were significantly higher in men than in women (p < 0.05). The mean values of PFp and PFd were similar in left and right feet (p > 0.05). There were moderate positive correlations between PFp and weight, height, and body mass index but no correlation between PFp and amount of athletic activity.

Conclusions

The thickness of the plantar fascia at origin did not change with athletic activity at the amateur level. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:17–21, 2006
In vivo electrogene transfer of interleukin‐12 inhibits tumor growth and lymph node and lung metastases in mouse mammary carcinomas
Authors: Shibata Masa‐Aki , Ito Yuko , Morimoto Junji , Kusakabe Ken , Yoshinaka Ryoji , Otsuki Yoshinori
Published: December 2005

Background

Human breast cancer metastasizes mainly to lymph nodes, lungs, liver, and bone; in the majority of cases, it is the development of metastases which leads to death. In order to suppress mammary cancer metastasis, we applied in vivo electrogene transfer (non‐viral method) as a means of interleukin‐12 (IL‐12) gene therapy on highly metastatic murine mammary cancer model.

Methods

Metastatic mammary tumors induced by inoculation in BALB/c female mice were treated by intratumoral injections of either a plasmid vector containing IL‐12 or empty vector and then subjected to in vivo electrogene transfer once a week for 8 weeks.

Results

Treatment with IL‐12 resulted in elevation of both IL‐12 and IFNγ levels in mammary tumors and in serum and intratumoral levels of CD4 and CD8 proteins were also increased. Tumor volumes and lymphatic and pulmonary metastases were significantly reduced. The histopathological changes induced by IL‐12 characteristically included marked inflammation, increased apoptosis, decreased DNA synthesis, peripheral influx of significantly greater numbers of active macrophages, and reduced blood microvessel density, and apoptotic vascular endothelial cells were frequently seen. Western blotting showed decreases in VEGFR‐3 of tumors exposed to IL‐12 gene therapy. In adjuvant immunofluorescence studies, the CD31‐positive endothelial cells of microvessels showed decreased VEGFR‐3 expression in IL‐12‐treated tumors. However, apparent alterations in VEGFR‐3 expression of podoplanin‐positive lymphatic endothelial cells were not observed in IL‐12‐treated tumors. Although recombinant IL‐12 did not inhibit tubular formation of human umbilical vein endothelial cells in a Matrigel assay, recombinant IFNγ did completely suppress the tubular formation.

Conclusions

In vivo electrogene transfer of IL‐12 exerts strong anti‐tumorigenic and anti‐metastatic effects likely due to T‐cell‐mediated immune responses as well as anti‐angiogenic action. Copyright © 2005 John Wiley & Sons, Ltd.
Repeat hepatectomy for recurrent colorectal liver metastases
Authors: Pessaux Patrick , Lermite Emilie , Brehant Olivier , Tuech Jean‐Jacques , Lorimier Gérard , Arnaud Jean‐Pierre
Published: December 2005

Purpose

Liver resection represents the best and potentially curative treatment for metastatic colorectal cancer (MCC) to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. The aim of this study was to determine the value of repeat liver resection for recurrent MCC and to analyze the factors that can predict survival.

Patients and Methods

From January 1992 to October 2002, 42 patients from a group of 168 patients resected for MCC were submitted to 55 repeat hepatectomies (42 second, 11 third, and 2 fourth hepatectomies). Records were retrospectively reviewed. The primary tumor was carcinoma of the colon in 26 patients and carcinoma of the rectum in 16 patients. Liver metastases were synchronous in 24 patients (57.1%).

Results

There were 25 men and 17 women with the mean age of 63.5 years (range: 34–80). There was no intraoperative or postoperative mortality. The morbidity rates were 9.5%, 14.3%, and 18.2% (P = 0.6) respectively after a first, second, or third hepatectomies. No patients needed reoperation. Operative duration was longer after a second or third hepatectomie than after a first hepatectomie without difference for operative bleeding. Overall 5‐year survivals were 33%, 21%, and 36% respectively after a first, second, or third hepatectomies. Factors of prognostic value on univariate analysis included serum carcinoembryonic antigen levels (P = 0.01) during the first hepatectomy, the presence of extrahepatic disease (P = 0.05) and tumor size larger than 5 cm (P = 0.04) during the second hepatectomie.

Conclusions

Repeat hepatectomies can provide long‐term survival rates similar to those of first hepatectomies. J. Surg. Oncol. 2006;93:1–7. © 2005 Wiley‐Liss, Inc.
Surgical technique for totally implantable access ports (TIAP) needs improvement: A multivariate analysis of 400 patients
Authors: Seiler Christoph M. , Frohlich Boris E. , Dorsam Ulrich J. , Kienle Peter , Buchler Markus W. , Knaebel Hanns‐Peter
Published: December 2005

Background

The objective of this study was to analyze factors that may have an impact on the failure rate of the surgical implantation technique for totally implantable access ports (TIAP) and to assess whether morbidity rates differ between a primarily successful surgical and a secondary Seldinger approach.

Methods

Four hundred consecutive patients receiving a primary TIAP in local anesthesia were included into this retrospective cohort study. A logistic regression‐model was used to evaluate reasons for failure of the TIAP method.

Results

Three hundred eighteen (79.5%) patients had a successful TIAP procedure, 82 patients were intraoperatively converted to a Seldinger technique. Reasons for failure were: correct positioning impossible n = 54, no or only an undersized vessel for insertion available n = 17, other reasons n = 11. Logistic regression analysis did not reveal any significant factor for failure of the primary surgical approach. In the group with primarily successful TIAP, 8 of 318 patients (3%) developed complications compared to 7 of 82 patients (9%) converted to a Seldinger technique.

Conclusion

Failure of the surgical approach for implanting totally implantable access ports is related to insertion and positioning. Conversion to a Seldinger technique results in a higher complication rate. A modified approach for surgical port placement should be considered in order to reduce complications. J. Surg. Oncol. 2006;93:24–29. © 2005 Wiley‐Liss, Inc.