bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphic amino acids at codons 9 and 37 of HLA‐DQB1 alleles may confer susceptibility to cervical cancer among Chinese women
Authors: Wu Yuping , Chen Yulong , Li Longyu , Cao Yicheng , Liu Zehuan , Liu Benrong , Du Zhengping , Zhang Yanling , Chen Shangwu , Lin Zhongqiu , Xu Anlong
Published: January 2006

Cervical cancer is strongly associated with the infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear HPV infection, some develop persistent infections that may lead to cancer, implying genetic susceptibility factors for malignant progression. To verify whether HLA class II DQB1 polymorphism is related to cervical cancer in Chinese population, HLA‐DQB typing was carried out by PCR‐SBT for 258 patients with cervical cancer and 284 healthy controls, and the allele frequencies were calculated. In this study, HLA‐DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected patients with cervical cancer compared with healthy controls (χ2 = 31.7452, p < 0.0001; χ2 = 12.7838, pc = 0.0066), but DQB1*050201 allele was significantly lower (χ2 = 26.2187, p < 0.0001). This result indicates that HLA‐DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and DQB1*050201 may contribute to the resistance to the development of cervical cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr at the same two positions, respectively. This finding implies that polymorphic amino acids at the putative antigen binding residues 9 and 37 of HLA‐DQB1 alleles may play an important role in the development of cervical cancer. © 2006 Wiley‐Liss, Inc.
Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis
Authors: Wadhwa Renu , Takano Syuichi , Kaur Kamaljit , Deocaris Custer C. , Pereira‐Smith Olivia M. , Reddel Roger R. , Kaul Sunil C.
Published: January 2006

Mortalin, also known as mthsp70/GRP75/PBP74, interacts with the tumor suppressor protein p53 and inactivates its transcriptional activation and apoptotic functions. Here, we examined the level of mortalin expression in a large variety of tumor tissues, tumor‐derived and in vitro immortalized human cells. It was elevated in many human tumors, and in all of the tumor‐derived and in vitro immortalized cells. In human embryonic fibroblasts immortalized with an expression plasmid for hTERT, the telomerase catalytic subunit, with or without human papillomavirus E6 and E7 genes, we found that subclones with spontaneously increased mortalin expression levels became anchorage‐independent and acquired the ability to form tumors in nude mice. Furthermore, overexpression of mortalin was sufficient to increase the malignancy of breast carcinoma cells. The study demonstrates that upregulation of mortalin contributes significantly to tumorigenesis, and thus is a good candidate target for cancer therapy. © 2006 Wiley‐Liss, Inc.
EMMPRIN‐induced MMP‐2 activation cascade in human cervical squamous cell carcinoma
Authors: Sier Cornelis F.M. , Zuidwijk Kim , Zijlmans Henry J.M.A.A. , Hanemaaijer Roeland , Mulder‐Stapel Adri A. , Prins Frans A. , Dreef Enno J. , Kenter Gemma G. , Fleuren Gert Jan , Gorter Arko
Published: January 2006

Tumor progression and recurrence of cervical cancer is associated with upregulation of matrix metalloproteinase 2 (MMP‐2). We evaluated the location, origin and activity of MMP‐2 in cervical squamous cell carcinomas in comparison with MT1‐MMP (MMP‐14), TIMP‐2 and extracellular matrix metalloproteinase inducer (EMMPRIN). Positive immunostaining for MMP‐2 in malignant cells was detected in 83% of the patients. Two patterns of tumor cell MMP‐2 staining were observed: either homogenous in all tumor cells or confined to the cells neighboring the stroma (tumor‐border staining pattern, TBS). Fluorescence in situ zymography showed active MMP‐2 mainly around tumor nodules displaying TBS. The MMP‐2 staining of TBS tumors correlated significantly with the presence of TIMP‐2 and MT1‐MMP, proteins involved in docking MMP‐2 to the cell surface and essential for MMP‐2 activation. In situ mRNA hybridization in TBS tumors demonstrated more abundant presence of MMP‐2 mRNA in neighboring myofibroblasts than in the adjacent tumor cells. Moreover, the TBS MMP‐2 pattern correlated with the presence of EMMPRIN (p = 0.023), suggesting that tumor cells induce MMP‐2 production in nearby stromal cells. This pro‐MMP‐2 could subsequently be activated on tumor cells via the presence of MT1‐MMP and TIMP‐2. The biological relevance of this locally activated MMP‐2 was underscored by the observation that only the TBS pattern of MMP‐2 significantly correlated with decreased survival. In conclusion, the colocalization of EMMPRIN, MT1‐MMP and TIMP‐2 in human cervical carcinomas seems to be involved in a specific distribution pattern of tumor cell bound MMP‐2, which is related with local proteolytic activity and therefore might be associated with worse prognosis of the patients. © 2006 Wiley‐Liss, Inc.
Combined prophylactic and therapeutic cancer vaccine: Enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA‐A2 mice
Authors: Qian Jiahua , Dong Yujun , Pang Yuk‐Ying S. , Ibrahim Ramy , Berzofsky Jay A. , Schiller John T. , Khleif Samir N.
Published: January 2006

We identified the strategies to induce a CTL response to human papillomavirus (HPV) 16 E2 in HLA‐A2 transgenic mice (AAD). A chimeric HPV16 virus‐like particle (VLP) that includes full length HPV16 E7 and E2 (VLP‐E7E2) was generated. The combination of E2 and E7 has the advantage that E2 is expressed in early dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions. Since T cell response to E2 is less defined, we first evaluated the strategies to enhancing CD8+ T cell responses to HPV E7, using different combinations of immune‐modulators with VLP‐E7E2. Data showed that the CTL response to E7 could be significantly enhanced by coinjection of GM‐CSF and antiCD40 antibodies with chimeric VLP‐E7E2 without adjuvant. However, using the same combination, a low level of CD8+ T cell response to E2 was detected. To enhance the CD8+ T cell response to E2, we analyzed T cell epitopes from E2 sequence. A heterogonous prime‐boost with chimeric VLP‐E7E2 and E2 peptides was performed. The data showed that the priming with chimeric VLP‐E7E2, followed by boosting with E2 peptides, gave a better CTL response than 2 immunizations with E2 peptides. The enhanced immunity is due to the increase of CD11c+ and CD11c+ CD40+ double positive dendritic cells in mice that received immune‐modulators, GM‐CSF and antiCD40. Furthermore, the level of anti‐L1 antibodies remains similar in mice immunized with chimeric VLP with/without immune‐modulators. Thus, the data suggested that the chimeric VLP‐E7E2 has a therapeutic potential for the treatment of HPV‐associated CINs and cancer without diminishing VLPs potential as a prophylactic vaccine by inducing anti‐L1 antibodies against free virus. © 2006 Wiley‐Liss, Inc.
Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer
Authors: Slattery Martha L. , Sweeney Carol , Murtaugh Maureen , Ma Khe‐Ni , Caan Bette J. , Potter John D. , Wolff Roger
Published: January 2006

The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association. © 2006 Wiley‐Liss, Inc.
HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD‐1 overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma
Authors: Geng Hui , Zhang Gui‐Mei , Xiao Han , Yuan Ye , Li Dong , Zhang Hui , Qiu Hui , He Yu‐Fei , Feng Zuo‐Hua
Published: January 2006

Many tumor immunotherapy efforts are focused on the generation of strong T‐cell response against tumor antigens. However, strong T‐cell response does not always coincide with tumor rejection, for which upregulated expression of immunoinhibitory molecules may be responsible. In this study, the treatment with heat shock protein 70 (HSP70) vaccine induced an infiltration of T cells into the tumor site as well as the expression of IFN‐γ and IL‐2, and delayed lung metastases of tumor, but the tumor progression nonetheless occur finally. We demonstrated that B7‐H1 expressed by residual tumor cells was responsible for the resistance of tumor to the therapy with HSP70 vaccine. Blockade of B7‐H1 by i.v. injection pPD‐1A, a plasmid encoding the extracellular domain of PD‐1 (sPD‐1), could reverse this resistance and enhance the therapeutic efficacy. To complement these findings, we investigated the gene expression of tumor‐infiltrating lymphocytes (TILs) by Real‐time PCR analysis, which revealed that the expression of TH1 cytokines IFN‐γ and IL‐2 by TIL in the mice treated with HSP70 vaccine in combination with sPD‐1 was increased and the expression of negative regulatory molecules IL‐10, TGF‐β and foxp3 was decreased, demonstrating that multifunctional properties afforded by the combination therapy can effectively overcome tumor resistance and promote effective antitumor immunity. The in vivo transfection with pPD‐1A could be performed as infrequently as once a week and still produce a significant antitumor effect. These findings suggest that the treatment with HSP70 vaccine followed by blockade of tumor‐B7‐H1 with sPD‐1 may provide a promising approach for tumor immunotherapy. © 2006 Wiley‐Liss, Inc.
Increased PTEN expression due to transcriptional activation of PPARγ by Lovastatin and Rosiglitazone
Authors: Teresi Rosemary E. , Shaiu Chung‐Wai , Chen Ching‐Shih , Chatterjee V. Krishna , Waite Kristin A. , Eng Charis
Published: January 2006

Germline mutations in the tumor suppressor genePTEN(protein phosphatase and tensin homolog located on chromosome ten) predispose to heritable breast cancer. The transcription factor PPARγ has also been implicated as a tumor suppressor pertinent to a range of neoplasias, including breast cancer. A putative PPARγ binding site in thePTENpromoter indicates that PPARγ may regulatePTENexpression. We show here that the PPARγ agonist Rosiglitazone, along with Lovastatin, induce PTEN in a dose‐ and time‐dependent manner. Lovastatin‐ or Rosiglitazone‐induced PTEN expression was accompanied by a decrease in phosphorylated‐AKT and phosphorylated‐MAPK and an increase in G1 arrest. We demonstrate that the mechanism of Lovastatin‐ and Rosiglitazone‐associated PTEN expression was a result of an increase inPTENmRNA, suggesting that this increase was transcriptionally‐mediated. Compound‐66, an inactive form of Rosiglitazone, which is incapable of activating PPARγ, was unable to elicit the same response as Rosiglitazone, signifying that the Rosiglitazone response is PPARγ‐mediated. To support this, we show, using reporter assays including dominant‐negative constructs of PPARγ, that both Lovastatin and Rosiglitazone specifically mediate PPARγ activation. Additionally, we demonstrated that cells lacking PTEN or PPARγ were unable to induce PTEN mediated cellular events in the presence of Lovastatin or Rosiglitazone. These data are the first to demonstrate that Lovastatin can signal through PPARγ and directly demonstrate that PPARγ can upregulate PTEN at the transcriptional level. Since PTEN is constitutively active, our data indicates it may be worthwhile to examine Rosiglitazone and Lovastatin stimulation as mechanisms to increase PTEN expression for therapeutic and preventative strategies including cancer, diabetes mellitus and cardiovascular disease. © 2006 Wiley‐Liss, Inc.
Prospective study of physical activity in different periods of life and the risk of ovarian cancer
Authors: Weiderpass Elisabete , Margolis Karen L. , Sandin Sven , Braaten Tonje , Kumle Merethe , Adami Hans‐Olov , Lund Eiliv
Published: January 2006

Only few studies have assessed the role of physical activity in the etiology of ovarian cancer, and the results have been inconclusive. We studied associations between physical activity and risk of ovarian cancer in 96,541 women aged 30–49 at enrollment in a prospective study in Norway and Sweden. Participants reported physical activity level at ages 14, 30 and at enrollment, and participation in competitive sports. Complete follow‐up through 2001/2002 was achieved by linkage to national registries. The relation between physical activity and ovarian cancer incidence was assessed using multivariate Cox proportional hazard models. During an average 11.1 years of follow‐up, there were 264 ovarian cancer cases (including 81 borderline tumors) diagnosed at a mean age of 49 years. Highly physically active women at cohort enrollment had a similar risk of ovarian cancer as women reporting no activity (multivariate relative risk RR = 1.08, 95% CI 0.53–2.18). Physical activity at age 30 or at age 14 did not either afford any protection from ovarian cancer, nor did a consistently high level of activity from younger ages until enrollment. Results were similar for invasive and borderline tumors, and for different subgroups of women classified according to other known risk factors for ovarian cancer. In our study of primarily premenopausal women, physical activity at different ages did neither reduce nor increase risk of ovarian cancer. In the context of the inconsistent scientific literature, our findings probably reflect that physical activity is not causally related with ovarian cancer. © 2006 Wiley‐Liss, Inc.
In vivo study of novel biodegradable and osteoconductive CaO‐SiO2‐B2O3 glass‐ceramics
Authors: Lee Jae Hyup , Lee Choon‐Ki , Chang Bong‐Soon , Ryu Hyun‐Seung , Seo Jun‐Hyuk , Hong Kug Sun , Kim Hwan
Published: January 2006

To evaluate the possibility of novel CaO‐SiO2‐B2O3 glass‐ceramics (CS10B) as a new bone replacement material, we compared the biodegradation and osteoconduction properties of CS10B, hydroxyapatite (HA), and tricalcium phosphate (TCP). Porous CS10B implants were prepared by the polymer sponge method. L5–6 single‐level posterolateral spinal fusions were performed on 30 New Zealand white male rabbits. The animals were divided into three groups by implant material: CS10B, HA, and TCP. Radiographs were performed every 2 weeks. All animals were euthanized 12 weeks after surgery. The ratio of the area occupied by the ceramics by final and initial radiographs was calculated using radiomorphometric analysis. Uniaxial tensile strength was determined from seven cases in each group. The ratio of the area occupied by HA (88.7% ± 16.1%) was significantly higher than the others (p < 0.005), and the ratio of the area occupied by CS10B (28.2% ± 9.3%) was significantly lower than those of HA and TCP (37% ± 9.6%, p < 0.05). The mean values of the tensile strengths of the CS10B (182.7 ± 19.9 N) and HA (191.4 ± 33.5 N) were significantly higher (p < 0.05) than that of TCP (141.1 ± 28.2 N). CS10B had a fusion mass tensile strength similar to that of HA. Histological analysis confirmed that CS10B was well incorporated into the fusion mass. These findings suggest that CS10B is a possible bone replacement material. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Simulation of a membrane bioreactor for regeneration of degreasing systems
Authors: Okoth George , Thöming Jorg , Schmidt Hans‐Jürgen
Published: January 2006

The dynamic behaviour of membrane bioreactors (MBRs) with negligible biomass growth due to the presence of toxic substances was modelled to simulate a pilot plant test in an industrial degreasing unit. Modelling was done by introducing a substrate biodegradation rate into a material balance equation of an MBR. This was followed by a discrimination procedure between the simulated and measured values, from which best‐fit specific substrate uptake rates (qsp) were determined at different air supply rates. The results showed clear improvement of qsp with increased air supply, indicating a possible increase in the active cell population in the reactor due to reduced toxicity. The highest specific substrate uptake rate (qsp = 0.08 gsubstrate gbiomass−1 d−1) determined was assumed equal to the maintenance coefficient (qm) for the biodegradation of the substrate under the test conditions. The understanding of the dynamics provided a reference in subsequent regeneration system improvement. Copyright © 2006 Society of Chemical Industry
Developmental mechanisms underlying tooth patterning in continuously replacing osteichthyan dentitions
Authors: Huysseune Ann , Witten P. Eckhard
Published: January 2006

The dentition of osteichthyans presents an astonishing diversity with regard to the distribution of teeth in the oral cavity, tooth numbers, arrangements, shapes, and sizes. Taking examples from three unrelated teleosts—the most speciose group of osteichthyans—and from the literature, this study explores how the initial tooth pattern is set up, and how this relates to the establishment and maintenance (or modification) of the tooth replacement pattern.

In teleosts, first‐generation teeth (the very first teeth in ontogeny to develop at a particular locus) are commonly initiated in adjacent or in alternate (odd and even) positions. The mechanisms responsible for these divergent developmental patterns remain to be elucidated, in particular, whether they reflect a field or local type of control. However, patterns of adjacent or alternate tooth initiation, set up by the first‐generation teeth, can easily turn into replacement patterns where new teeth are initiated simultaneously every second, or even every third position, by synchronizing the formation of new first‐generation teeth to the formation of replacement teeth at older loci.

Our observations suggest that, once established, the replacement pattern appears to be maintained, as a kind of “default” state. Variations and modifications in this pattern are nevertheless common and suggest that tooth replacement is under local control, exerted at the level of the initiation of replacement teeth. Further studies are needed to test the hypothesis that regular replacement patterns are more frequent in association with the plesiomorphic condition of extramedullary replacement (replacement on the surface of the dentigerous bone) and more rare in the derived condition of intramedullary replacement (replacement within the medullary cavity of the dentigerous bone). J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2006 Wiley‐Liss, Inc.
Antioxidant capacity of methanolic and water extracts prepared from food‐processing by‐products
Authors: Amin I , Mukhrizah O
Published: January 2006

This study aims to evaluate the antioxidant capacity of mango peel, roselle seed, okara (by‐product of soya milk industry), cocoa shell and pink guava (by‐product of pink guava industry) in comparison to 6‐hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox). The β‐carotene bleaching, 1,1‐diphenyl‐2‐picrylhydrazyl and reducing power assays were used to determine the antioxidant capacity of selected by‐products by measuring the absorbance at 470, 520 and 700 nm, respectively. The results showed that methanolic extracts of pink guava and cocoa shell exhibited the highest antioxidant activity and free radical scavenging activity compared to other studied samples. Roselle seed water extract exhibited the highest antioxidant activity and free radical scavenging when extracted with water. Pink guava possessed the highest reducing power in methanolic extract at a concentration of 0.16 mg mL−1. At the same concentration, mango peel exhibited the highest reducing power when extracted with water. The present study shows that pink guava, roselle seed and cocoa shell are potential sources of antioxidant components that can be exploited as food preservative agents or nutraceuticals. Copyright © 2006 Society of Chemical Industry
Investigation of the effect of sumac extract and BHT addition on the quality of sucuk (Turkish dry‐fermented sausage)
Authors: Bozkurt Hüseyin
Published: January 2006

The effect of sumac extract and BHT (butylated hydroxytoluene) addition on the quality (pH, colour, biogenic amine, TBARS values and sensory attributes) of sucuk (Turkish dry‐fermented sausage) were investigated during the ripening period. Addition of BHT decreased the TBARS value by about 23.7%, whereas sumac extract decreased it by 42.0%. Sumac extract decreased (P < 0.05) putrescine formation more than BHT addition. However, no significant difference (P > 0.05) was observed in histamine formation for both the sumac extract and BHT‐added recipe. The highest tyramine concentration was observed in a control recipe (R1) prepared without any antioxidants, and the lowest was in the sumac extract‐added recipe (R3) with mean values of about 96.62 and 63.17 mg kg−1, respectively. The control recipe (R1) was found to be the worst (P < 0.05) sample with respect to overall sensory quality and addition of either sumac extract or BHT increased (P < 0.05) the overall sensory quality of sucuk. The pH and colour attributes of sucuk were not significantly different (P > 0.05) between the addition of sumac extract and BHT. This study demonstrated that sumac extract had more effect on the quality of sucuk during the ripening period, hence it could be easily utilised in sucuk to enhance quality. Copyright © 2006 Society of Chemical Industry
Synthesis of Polypyrrole Using Benzoyl Peroxide as a Novel Oxidizing Agent
Authors: Saravanan Chandrasekaran , Shekhar Rampally Chandra , Palaniappan Srinivasan
Published: January 2006

Summary: Benzoyl peroxide is used as an oxidizing agent for the first time in the synthesis of conducting polypyrrole. Synthesis of polypyrrole is commonly performed by chemical oxidative polymerization using water‐soluble oxidizing agents. In this work, polypyrrole was prepared using organic solvent‐soluble benzoyl peroxide as an oxidizing agent in the presence of p‐toluenesulfonic acid (p‐TSA) and sodium lauryl sulfate (SLS) surfactant via the inverted‐emulsion‐polymerization technique. During polymerization, SLS is converted to dodecyl hydrogensulfate (DHS) and incorporated on to polypyrrole along with p‐TSA dopant, indicating SLS is acting as emulsifier as well as dopant. The influence of synthesis conditions such as the duration of the reaction, the temperature, the concentration of the reactants, etc., on the properties of polypyrrole was investigated to determine the optimum conditions for the synthesis of polypyrrole salt. Polypyrrole was obtained in a reaction time of 1 h with high yield (154 wt.‐% with respect to pyrrole used) and good conductivity (2 S · cm−1). The conductivity of polypyrrole‐salt was found to be nearly the same even after seven months of storage at ambient temperature (1.7 S · cm−1).

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Evolution of the Morphology and Characterization of Compatibilized PBT/EVA Blends Prepared by Reactive Extrusion
Authors: Scaffaro Roberto , La Mantia Francesco Paolo
Published: January 2006

Summary: In this work, the possibility of preparing compatibilized blends of poly(butylene terephthalate) (PBT) and an ethylene vinyl acetate (EVA) copolymer by reactive extrusion in the presence of an ethylene acrylic acid copolymer (EAA) and a bisoxazoline compound (PBO) as compatibilization promoters has been studied. In addition, the evolution of the morphology of the blends under different annealing conditions in the presence and absence of the compatibilizing promoters has been studied. Binary blends of PBT and EVA showed behavior typical of incompatible blends with a gross morphology and bad mechanical performance. The situation was however different for ternary PBT/EVA/EAA and especially for quaternary PBT/EVA/EAA/PBO blends. In the latter case, the morphology was finer, the adhesion improved and the mechanical properties were enhanced, with values almost doubled with respect to those of uncompatibilized blends. These results can be explained by the formation of in situ EAA‐g‐(PBO)PBT copolymers which act as compatibilizers for the blends. While the binary and, to some extent, the ternary blend display coalescence under annealing with rapid coarsening of the morphology, the quaternary compatibilized blends showed the best morphological stability as the particle dimensions remained practically unchanged. This phenomenon was interpreted considering the role of kinetic hindrance played by the compatibilizer formed in situ.

SEM micrograph of PBT/EVA/EAA/PBO blend at 5 000×.

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SEM micrograph of PBT/EVA/EAA/PBO blend at 5 000×.
Chemoprevention of lung cancer by tea
Authors: Clark Julie , You Ming
Published: January 2006

Tea is the second only to water as the most consumed beverage in the world. Both green and black teas have been studied for their health benefits for a variety of diseases, particularly cancer. Lung cancer is the predominant cause of cancer mortality in developed countries. Smokers’ risk of lung cancer is 20 times that of persons who have never smoked. Epidemiological studies on the cancer‐preventive effects of tea produce inconsistent results, which could in part be attributed to the lack of a universal standard for tea preparations. However, most animal studies indicate that tea has strong chemopreventive effects against lung tumorigenesis. The reported mechanisms for chemopreventive activity of green tea are antioxidation, induction of phase II enzymes, inhibition of TNFα expression and release, inhibition of cell proliferation, and induction of apoptosis. Cell cycle arrest and apoptosis induced by green tea are probably the two most significant factors. Future studies are needed to determine how green tea affects the genes associated with cell cycle regulation and apoptosis during the mouse lung carcinogenesis process.
The matricellular protein SPARC is internalized in Sertoli, Leydig, and germ cells during testis differentiation
Authors: Wilson Megan J. , Bowles Josephine , Koopman Peter
Published: January 2006

The gene encoding the matricellular protein secreted protein, acidic and rich in cysteine (SPARC) was identified in a screen for genes expressed sex‐specifically during mouse gonad development, as being strongly upregulated in the male gonad from very early in testis development. We present here a detailed analysis of SPARC gene and protein expression during testis development, from 11.5 to 15.5 days post coitum (dpc). Section in situ hybridization analysis revealed that SPARC mRNA is expressed by the Sertoli cells in the testis cords and the fetal Leydig cells, found within the interstitial space between the testis cords. Immunodetection with anti‐SPARC antibody showed that the protein was located inside the testis cords, within the cytoplasm of Sertoli and germ cells. In the interstitium, SPARC was present intracellularly within the Leydig cells. The internalization of SPARC in Sertoli, Leydig, and germ cells suggests that it plays an intracellular regulatory role in these cell types during fetal testis development. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Ca2+ and Na+ current patterns during oocyte maturation, fertilization, and early developmental stages of Ciona intestinalis
Authors: Cuomo Annunziata , Silvestre Francesco , De Santis Rosaria , Tosti Elisabetta
Published: January 2006

Using the whole‐cell voltage clamp technique, the electrical changes in oocyte and embryo plasma membrane were followed during different meiotic and developmental stages in Ciona intestinalis. We show, for the first time, an electrophysiological characterization of the plasma membrane in oocytes at the germinal vesicle (GV) stage with high L‐type calcium (Ca2+) current activity that decreased through meiosis. Moreover, the absence of Ca2+ reduced germinal vesicle breakdown (GVBD), which is consistent with a role of Ca2+ currents in the prophase/metaphase transition. In mature oocytes at the metaphase I (MI) stage, Ca2+ currents decreased and then disappeared and sodium (Na+) currents first appeared remaining high up to the zygote stage. Intracellular Ca2+ release was higher in MI than in GV, indicating that Ca2+ currents in GV may contribute to fill the stores which are essential for oocyte contraction at fertilization. The fertilization current generated in Na+ free sea water was significantly lower than the control; furthermore, oocytes fertilized in the absence of Na+ showed high development of anomalous “rosette” embryos. Current amplitudes became negligible in embryos at the 2‐ and 4‐cell stage, suggesting that signaling pathways that mediate first cleavage do not rely on ion current activities. At the 8‐cell stage embryo, a resumption of Na+ current activity and conductance occurred, without a correlation with specific blastomeres. Taken together, these results imply: (i) an involvement of L‐type Ca2+ currents in meiotic progression from the GV to MI stage; (ii) a role of Na+ currents during electrical events at fertilization and subsequent development; (iii) a major role of plasma membrane permeability and a minor function of specific currents during initial cell line segregation events. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Salivary gland neoplasms in children: The experience of the Istituto Nazionale Tumori of Milan
Authors: Guzzo Marco , Ferrari Andrea , Marcon Ilaria , Collini Paola , Gandola Lorenza , Pizzi Natalia , Casanova Michela , Mattavelli Franco , Scaramellini Gabriele
Published: January 2006

Background

Epithelial salivary gland tumors are very uncommon in pediatric age. We report a series of 52 cases treated at the Istituto Nazionale Tumori of Milan, Italy, over a 30‐year period. These results are presented in conjunction with a literature review of salivary tumors with a view to providing an up‐to‐date overview of the clinical course, prognosis, and treatment options for this rare tumor.

Procedure

Fifty‐two cases of epithelial salivary tumors were reviewed and the clinical‐pathological information concerning tumor characteristics, therapy, and follow‐up were collected. Patients' age ranged between 4 and 18 years.

Results

The major salivary glands were the main site of tumor occurrence (79% of cases arose in parotid glands); 37 patients had benign tumors (pleomorphic adenoma), 15 had malignant tumors (12 mucoepidermoid carcinoma, 9 low grade). All the patients were treated by surgery; local relapses after parotidectomy were 4% and 25%, in benign and malignant tumors, respectively. When tumor enucleation was performed, recurrences occurred in 50% of benign neoplasms. At the time of the report, all patients with benign tumors were alive, 35(95%) without evidence of disease; only one patient with malignant tumor died of disease.

Conclusions

Epithelial salivary glands tumor in children had different characteristics compared with their adult counterpart with respect to the frequency of histotypes and site of occurrence, but their prognosis seems to be similar. Parotidectomy (total or superficial) is the best choice for achieving good cure rates in both benign and malignant tumors. Pediatric Blood Cancer 2006;47:806–810. © 2006 Wiley‐Liss, Inc.
Asparagine depletion after pegylated E. coli asparaginase treatment and induction outcome in children with acute lymphoblastic leukemia in first bone marrow relapse: A Children's Oncology Group study (CCG‐1941)
Authors: Jarrar Mohammad , Gaynon Paul S. , Periclou Antonia P. , Fu Cecilia , Harris Richard E. , Stram Daniel , Altman Arnold , Bostrom Bruce , Breneman John , Steele David , Trigg Michael , Zipf Theodore , Avramis Vassilios I.
Published: January 2006

Purpose

Re‐induction outcomes vary for children with acute lymphoblastic leukemia (ALL) and marrow relapse. We explored possible relationships among asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti‐ASNase antibody titers, and response to re‐induction therapy in children and adolescents with ALL and an ‘early’ first marrow relapse.

Patients and methods

After appropriate informed consent, we enrolled children and adolescents 1–21 years old with ALL and first marrow relapse within 12 months of completion of primary therapy. Induction therapy included intramuscular pegylated ASNase on Days 2 and 16. We assessed ASNase activity, anti‐ASNase antibody titers against native and pegylated (E. coli) ASNase, and amino acid levels of asparagine (ASN) and glutamine (GLN) on Days 0, 14, and 35 of re‐induction.

Results

Ninety‐three patients were at least partially assessable. Among 21 patients with M1 marrow status at Day 35, the median Day 14 ASN level was <1 µM. This is significantly lower than the median Day 14 ASN level of 4 µM in the group of patients with M3 marrow at Day 35. Neither Day 0 nor Day 35 antibody titers predicted ASNase enzymatic activity level on Day 14. Surprisingly, Day 14 ASNase activity did not predict serum ASN level on Day 14. However, Day 0 and Day 35 anti‐native ASNase antibody titers, and Day 0 anti‐PEG ASNase antibody titers correlated positively with Day 14 serum ASN levels as one might expect from neutralizing antibody. Day 35 anti‐PEG ASNase antibody titers did not.

Conclusions

Patients with greater ASN depletion were more likely to achieve second remission in the context of six‐drug therapy. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
The return of research results to participants: Pilot questionnaire of adolescents and parents of children with cancer
Authors: Fernandez C.V. , Santor D. , Weijer C. , Strahlendorf C. , Moghrabi A. , Pentz R. , Gao J. , Kodish E.
Published: January 2006

Purpose

The offer to return research results to participants is increasingly recognized as an ethical obligation, although few researchers routinely return results. We examined the needs and attitudes of parents of children with cancer and of adolescents with cancer to the return of research results.

Methods

Seven experts in research ethics scored content validity on parent and adolescent questionnaires previously developed through focus group and phone interviews. The questionnaires were revised and provided to 30 parents and 10 adolescents in a tertiary care oncology setting.

Results

The content validity index for individual questions and the overall questionnaires scored as 0.86 for both questionnaires. All 30 parents and 10 adolescents who agreed to participate returned questionnaires. The majority (>95%) indicated that they had a strong or very strong right to receive results. Letter or e‐mail was a satisfactory means to return results described as good or neutral (66% parents, 100% adolescents) but more participants wished face‐to‐face disclosure of results with negative implications (50% parents, 60% adolescents). Very few wanted results disseminated through a Web site. The majority acknowledged the need for peer‐review before disclosure (60% of adolescents and parents) but did not want “to be the last to know.”

Conclusions

Our data suggest that pediatric oncology patients and parents of children with cancer strongly feel that they have a right to research results, and that they wish to receive these in a timely manner. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Classification of malignant pediatric renal tumors by gene expression
Authors: Huang Chiang‐Ching , Cutcliffe Colleen , Coffin Cheryl , Sorensen Poul H. B. , Beckwith J. Bruce , Perlman Elizabeth J.
Published: January 2006

Background

The most common malignant renal tumors of childhood are Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), cellular mesoblastic nephroma (CMN), and rhabdoid tumor of the kidney (RTK). Because these tumors present significant diagnostic difficulties, the goal was to define diagnostically useful signatures based on gene expression.

Procedures

Gene expression analysis using oligonucleotide arrays was performed on a training set of 47 tumors (10 CCSKs, 9 CMNs, 8 RTKs, and 20 WTs). Classifiers were developed for each tumor type using variations of compound covariate class predictor. The classifiers were applied to an independent test set of 72 tumors (3 CMN, 7 CCSK, 4 RTK, and 58 WT). Central review diagnosis was utilized as the gold standard. Correlation with the institutional diagnosis and qualitative estimation of confidence levels at the time of central review were noted.

Results

Within the training set, classifiers resulted in no errors when >10 genes were utilized. Top genes in each classifier were verified using quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). Applying the classifiers to the test set, 71 of 72 tumors were correctly classified with a confidence level of >99%. The exception was incorrectly classified by the gold standard. In comparison, by histopathology 31% of the non‐WT were not accurately classified by the local institution, and 29% were classified with <95% confidence on central review.

Conclusions

Classifiers based on gene expression provide diagnostic confidence and accuracy greater than that of pathologic analysis alone. Tumors that show ambiguous gene expression profiles are those that are also pathologically and molecularly ambiguous and merit further analysis. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Characterization of plasma gelsolin as a substrate for matrix metalloproteinases
Authors: Park Sung‐Min , Hwang In Kwan , Kim Se Yeon , Lee Seo‐Jin , Park Kang‐Sik , Lee Seung‐Taek
Published: January 2006

We previously showed that plasma gelsolin, a major component of the extracellular actin scavenging system, is an matrix metalloproteinase (MMP)‐14 substrate. Here we confirmed that plasma gelsolin is cleaved by MMP‐14 at the plasma level, and found that it was most efficiently digested by MMP‐3 followed by MMP‐2, MMP‐1, MMP‐14, and MMP‐9, in that order. Plasma gelsolin (90 kDa) was cut into several fragments of 43–48 kDa by MMP‐3. The MMP‐3 cleavage sites in plasma gelsolin were determined by labeling the C termini generated by in‐gel digestion with 50% H218O combined with peptide mass mapping, and sequencing of the N‐terminal amino acids. Plasma gelsolin was cleaved at Asn416‐Val417, Ser51‐Met52, and Ala435‐Gln436.Proteolytic cleavage by MMP‐3 resulted in considerable loss of its actin filament‐depolymerizing activity. This suggests that MMPs weaken the extracellular actin‐scavenging system by cleaving plasma gelsolin and may, therefore, be involved in pathological conditions induced by extracellular actin, such as endothelial injury, respiratory distress syndrome, hepatic necrosis, and septic shock.
Identification of an anti‐aldolase autoantibody as a diagnostic marker for diabetic retinopathy by immunoproteomic analysis
Authors: Ahn Bo‐Young , Song Eun‐Sun , Cho Yang Je , Kwon Oh Woong , Kim Jin Kook , Lee Na Gyong
Published: January 2006

Circulating autoantibodies specific for retinal proteins are associated with retinal destruction in patients with diabetic retinopathy (DR). In this study, we screened diabetic sera for the presence of anti‐retinal autoantibodies with an aim of developing diagnostic markers for DR. Immunoblot analysis of DR patients' sera with human retinal cytosolic proteins revealed a higher incidence of anti‐retinal autoantibodies, compared to normal blood donors or diabetic patients without DR. Anti‐retinal protein autoantibody profiles of DR patient sera were obtained by 2‐DE immunoblot analysis. Specifically, 20 protein spots reactive with DR patient sera were identified by ESI‐MS/MS. Of these spots, 14 were specific for DR patients, and 4 reacted with both non‐proliferative DR (non‐PDR) and PDR sera. The anti‐aldolase autoantibody was selected as a DR marker candidate, and specific reactivity of DR patient sera was confirmed by immunoblot analysis with rabbit aldolase. The serum anti‐aldolase autoantibody level was measured by ELISA. DR patients showed significantly higher autoantibody levels than normal donors or diabetic patients without retinopathy. However, no significant differences were observed between non‐PDR and PDR patients, suggesting that the level of anti‐aldolase autoantibody is not determined by the severity of retinopathy in diabetic patients. Our data collectively demonstrate that the anti‐aldolase autoantibody serves as a useful marker for DR diagnosis.
Linker chains of the gigantic hemoglobin of the earthworm Lumbricus terrestris: Primary structures of linkers L2, L3, and L4 and analysis of the connectivity of the disulfide bonds in linker L1
Authors: Kao Wen‐Yen , Qin Jun , Fushitani Kenzo , Smith Sandra S. , Gorr Thomas A. , Riggs Claire K. , Knapp James E. , Chait Brian T. , Riggs Austen F.
Published: January 2006

The extracellular hemoglobin (Hb) of the earthworm, Lumbricus terrestris, has four major kinds of globin chains: a, b, c, and d, present in equimolar proportions, and additional non‐heme, non‐globin scaffolding chains called linkers that are required for the calcium‐dependent assembly of the full‐sized molecule. The amino acid sequences of all four of the globin chains and one of the linkers (L1) have previously been determined. The amino acid sequences via cDNA of each of the three remaining linkers, L2, L3, and L4, have been determined so that the sequences of all constituent polypeptides of the hemoglobin are now known. Each linker has a highly conserved cysteine‐rich segment of ∼ 40 residues that is homologous with the seven ligand‐binding repeats of the human low‐density lipoprotein receptor (LDLR). Analysis of linker L1 shows that the connectivity of the three disulfide bonds is exactly the same as in the LDLR ligand‐binding repeats. The presence of a calcium‐binding site comprising one glutamyl and three aspartyl residues in both the LDLR repeats and in the linkers supports the suggestion that calcium is required for the folding and disulfide connectivity of the linkers as in the LDLR repeats. Linker L2 is markedly heterogeneous and contains unusual glycine‐rich sequences near the NH2‐terminus and a polar zipper‐like sequence with imperfect repeats of Asp‐Asp‐His at the carboxyl terminus. Similar Asp‐Asp‐His repeats have been found in a protein homologous to superoxide dismutase in the hemolymph of certain mussels. These repeats may function as metal‐binding sites. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Wind lidar evaluation at the Danish wind test site in Høvsøre
Authors: Smith David A. , Harris Michael , Coffey Adrian S. , Mikkelsen Torben , Jørgensen Hans E. , Mann Jakob , Danielian Régis
Published: January 2006

Initial assessments of a wind lidar have shown the technology to have significant potential for wind field measurements in the wind energy industry. A more extended evaluation is now reported using a scanning lidar next to a meteorological mast with calibrated anemometers at the Risø wind test site in Høvsøre on the windy northwest coast of Denmark. Results are presented of wind speed comparisons at heights up to 100 m above ground level showing excellent correlation between the lidar and the cup anemometers. Copyright © 2006 John Wiley & Sons, Ltd.
Effects of selective excitation of x‐ray fluorescence of light elements: fluorine, oxygen, nitrogen and carbon
Authors: Dukhanin A. Y. , Pavlinsky G. V.
Published: January 2006

This paper describes three variants of the selective excitation of elements with low atomic number, i.e. fluorine, oxygen, nitrogen and carbon. One of the variants considers intra‐atomic cascade transitions in the elements of the enclosing matrix. Selective excitation effect values were calculated with consideration of atom excitation by photo‐ and Auger electrons, originating in the material irradiated. It is shown that in some cases the total input of the effects of selective excitation amounts to a few tens of percent of the analytical signal intensity. This study also examines x‐ray fluorescence excitation by irradiating x‐ray tubes with different anodes and varying beryllium window thickness. Copyright © 2006 John Wiley & Sons, Ltd.
The antecedents and consequences of autonomous self‐regulation for college: A self‐determination theory perspective on socialization
Authors: Niemiec Christopher P. , Lynch Martin F. , Vansteenkiste Maarten , Bernstein Jessey , Deci Edward L. , Ryan Richard M.
Published: January 2006

Using self‐determination theory, two studies investigated the relations among perceived need support from parents, their adolescents’ autonomous self‐regulation for academics, and the adolescents’ well‐being. Study 1 indicated that perceived need support from parents independently predicted adolescents’ well‐being, although when mothers’ and fathers’ data were examined separately, the relation was stronger for mothers than for fathers. In Study 2, autonomous self‐regulation for planning to attend college was a significant partial mediator of the relation of adolescents’ perceived need support to well‐being. Thus, perceived need support from parents does seem important for the development of adolescents’ autonomous self‐regulation and well‐being.
Antipsychotic type and correlates of antipsychotic treatment discontinuation in the outpatient treatment of schizophrenia
Authors: Haro Josep Maria , Novick Diego , Belger Mark , Jones Peter B.
Published: January 2006

Antipsychotic medication maintenance and the factors influencing it were analyzed using data from the SOHO study, a large observational study of the outcomes of antipsychotic treatment for schizophrenia in Europe. A total of 7186 adult patients in the outpatient setting who were initiating or changing their antipsychotic medication and who were prescribed only one antipsychotic after the baseline visit were analyzed. Medication maintenance at 12 months varied with the type of antipsychotic prescribed, being highest with clozapine (79.5%) and olanzapine (77.0%), and lowest with quetiapine (51.4%) and amisulpride (58.2%). Multiple logistic regression analysis demonstrated that the type of antipsychotic prescribed at baseline was the most important predictor of medication maintenance. Alcohol dependency, taking mood stabilizers, compulsory admission or arrest in the previous 6 months, greater clinical severity, and changing antipsychotic medication due to lack of effectiveness at baseline predicted a higher frequency of medication discontinuation in the subsequent 12 months. In contrast, medication maintenance was higher among patients who were treatment naïve at baseline, socially active or who had loss of libido at baseline. The findings from this study should be interpreted conservatively because of its non-randomized observational design.