bluuebunny/crossref_metadata_2025_split huggingface dataset:
MSI phenotype and MMR alterations in familial and sporadic gastric cancer
Authors: Leite Marina , Corso Giovanni , Sousa Sónia , Milanezi Fernanda , Afonso Luís P. , Henrique Rui , Soares José Manuel , Castedo Sérgio , Carneiro Fátima , Roviello Franco , Oliveira Carla , Seruca Raquel 
Published: June 2010

AbstractMicrosatellite instability (MSI) is a major pathway involved in gastric carcinogenesis occurring in 20% of gastric cancer (GC). However, it is not clear whether MSI phenotype preferentially occurs in the sporadic or familial GC, when stringent inclusion criteria are used. The aim of this study was to compare the frequency of MSI and hypermethylation of MLH1 promoter in a large series of familial GC patients (non‐HNPCC and non‐CDH1‐related) and sporadic cases. Additionally, we analysed the immunoexpression of MMR proteins in a fraction of cases. Overall, the frequency of familial GC was 7.1%, and the frequency of hereditary tumours was 4.6%. MSI phenotype and MLH1 hypermethylation frequencies were not statistical different between familial and sporadic GC settings. Further, the MSI phenotype was not associated with any clinico‐pathological features studied in the familial GC setting, whereas in the sporadic setting, it was associated with older age, female gender and intestinal histotype. Using our stringent Amsterdam‐based clinical criteria to select familial GC (number of cases, age of onset), we verified that sporadic and familial cases differed in gender but shared histopathological features. We verified that the frequency of MSI was similar in familial and sporadic GC settings, demonstrating that this molecular phenotype is not a hallmark of familial GC in contrast to what is verified in HNPCC. Moreover, we observed that the frequency of MLH1 hypermethylation is similar in sporadic and familial cases suggesting that in both settings MSI is not associated to MMR genetic alterations but in contrast to epigenetic deregulation.
Dietary vitamin D intake and serum 25‐hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients
Authors: Meyer François , Liu Geoffrey , Douville Pierre , Samson Élodie , Xu Wei , Adjei Araba , Bairati Isabelle 
Published: June 2010

AbstractLow pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites. Its prognostic significance in head and neck cancer (HNC) patients has not been studied. Patients with HNC who participated in a randomized trial were evaluated for: (i) total intake of vitamin D from diet and supplements using a validated food frequency questionnaire (all trial participants, n = 540) and (ii) pretreatment serum 25‐hydroxyvitamin D through a radioimmunoassay (n = 522). The association of dietary/serum measures of vitamin D status with HNC recurrence, second primary cancer (SPC) incidence, and overall mortality was evaluated using multivariate Cox proportional hazard models. There was no significant association between dietary or serum vitamin D measures and the three HNC outcomes. The hazard ratios (HRs) comparing the highest with the lowest quartile of dietary/supplemental vitamin D intake were 1.10 (95% confidence interval (CI): 0.66–1.84) for recurrence, 1.05 (95% CI: 0.63–1.74) for SPC, and 1.27 (95% CI: 0.87–1.84) for overall mortality. HRs comparing the uppermost to the lowest quartile of serum 25‐hydroxyvitamin D levels were 1.12 (95% CI: 0.65–1.93) for recurrence, 0.72 (95% CI: 0.40–1.30) for SPC, and 0.85 (95% CI: 0.57–1.28) for overall mortality. There was no effect modification by cancer stage, season of initial treatment, or trial arm. Among patients with HNC, vitamin D status before treatment does not influence disease outcomes. Our results contrast with those from most published studies, which suggest prognostic significance of vitamin D status in cancer patients at least in subgroups.
Vitamin K enhancement of sorafenib‐mediated HCC cell growth inhibition in vitro and in vivo
Authors: Wei Gang , Wang Meifang , Hyslop Terry , Wang Ziqiu , Carr Brian I. 
Published: June 2010

AbstractThe multikinase inhibitor sorafenib is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including sorafenib as well as by the naturally occurring K vitamins (VKs). As few nontoxic agents have activity against HCC growth, we evaluated the activity of sorafenib and VKs, both independently and together on the growth of HCC cells in vitro and in vivo. We found that when VK was combined with sorafenib, the concentration of sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus sorafenib that were ineffective with either agent alone, using vitamins K1, K2 and K5. Combination of VK1 plus sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho‐extracellular signal‐regulated kinase (ERK) levels were decreased as was myeloid cell leukemia sequence 1 (Mcl‐1), an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At subeffective sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho‐ERK and Mcl‐1 staining. Thus, combination of VK1 plus sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/mitogen‐activated protein kinase kinase/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf: sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. As both agents are available for human use, the combination has potential for improving sorafenib effects in HCC.
Risk of endometrial cancer for women diagnosed with HNPCC‐related colorectal carcinoma
Authors: Obermair Andreas , Youlden Danny R. , Young Joanne P. , Lindor Noralane M. , Baron John A. , Newcomb Polly , Parry Susan , Hopper John L. , Haile Robert , Jenkins Mark A. 
Published: June 2010

AbstractThe risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non‐polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non‐Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10‐year cumulative risk of EC subsequent to CRC was 23.4% [95% confidence interval (CI): 15–36%] for Lynch syndrome women compared with 1.6% (95% CI: 0.7–3.8%) for non‐Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non‐Lynch women (HR 6.2; 95% CI 2.2–17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome‐associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.
Volumetric DXA (VXA): A new method to extract 3D information from multiple in vivo DXA images
Authors: Ahmad Omar , Ramamurthi Krishna , Wilson Kevin E , Engelke Klaus , Prince Richard L , Taylor Russell H 
Published: June 2010

Abstract
Three-dimensional geometric and structural measurements of the proximal femur are of considerable interest in understanding the strength of the femur and its susceptibility to fracture. Quantitative computed tomography (QCT) with a small voxel size (≤1 mm per side) is the current “gold standard” to examine the macrostructure of the femur, but it has a high effective radiation dose (approximately 2 to 5 mSv) and cost. Volumetric dual-energy X-ray absorptiometry (VXA) uses a commercially available DXA system (Hologic Discovery A) to reconstruct the proximal femur from four DXA scans delivering an effective radiation dose of 0.04 mSv. VXA was compared with QCT (voxel size of 0.29 × 0.29 × 1 mm) in 41 elderly women (age 82 ± 2.4 years) at slices located at the femoral neck and trochanteric regions of interest. For parameters of shape, the femoral neck axis length (FNAL) and the cross-sectional slice area (SA), accuracy and strong linear correlations (r = 0.84 to 0.98) were demonstrated. Similar correlations (r = 0.81 to 0.97) were observed for the density parameters, the cross-sectional bone area (CSA) and volumetric bone mineral density (vBMD). VXA also demonstrated strong correlations (r = 0.76 to 0.99) for the engineering parameters of the minimum, maximum, and polar cross-sectional moments of inertia (CSMIs) and the section modulus (Z). We conclude that VXA is capable of generating a variety of 3D geometric and structural measurements that are highly correlated with QCT in elderly subjects in vivo. Moreover, the VXA measurements can be made with a commercially available DXA device at a very low radiation dose. © 2010 American Society for Bone and Mineral Research.
Physical activity slows femoral bone loss but promotes wrist fractures in postmenopausal women: A 15-year follow-up of the OSTPRE study
Authors: Rikkonen Toni , Salovaara Kari , Sirola Joonas , Kärkkäinen Matti , Tuppurainen Marjo , Jurvelin Jukka , Honkanen Risto , Alhava Esko , Kröger Heikki 
Published: June 2010

Abstract
Results on fracture risk among physically active persons are contradictory. The aim of this study was to investigate the long-term association between the self-reported physical activity (PA), the risk of fractures, and bone loss among peri- and postmenopausal women. The association between PA and fracture risk was examined during 15 years of follow-up in the population-based Osteoporosis Risk Factor and Prevention (OSTPRE) Study among 8560 women with a mean age of 52.2 years (range 47 to 56 years) at baseline. The amount and type of PA, as well as the types and mechanisms of fractures, were registered with self-administered questionnaires at 5-year intervals (ie, 1989, 1994, 1999, and 2004). A total of 2641 follow-up fractures were verified in 2073 women (24.2%). The study cohort was divided into quartiles by average hours of reported PA during the whole follow-up. Areal bone mineral density (aBMD) at the proximal femur (n = 2050) and lumbar spine (L2–L4; n = 1417) was followed at 5-year intervals from a random stratified subsample with dual X-ray absorptiometry (DXA). Risk of fracture was estimated by using the Cox proportional hazards model with a mean follow-up time of 15.2 years. Weekly average time spent on leisure-time PA was 0.4, 1.7, 3.3, and 7.0 hours from the least to the most active quartiles, respectively. The risk of wrist fracture was higher in the active quartiles (II to IV) than in the most inactive quartile (I), with hazard ratios (HRs) of 1.3 [95% confidence interval (CI) 1.05–1.57, p = .014] for the second (II), 1.2 (95% CI 1.01–1.51, p = .045) for the third (III), and 1.4 (95% CI 1.14–1.69, p = .001) for the fourth (IV) quartile, respectively. Overall, most of the fractures were reported as a result of a fall (69.0%), with a 2.1 times higher rate of wrist fractures during the winter (November to April) than during summer season. There were no significant associations of PA with any other fracture types. Bone loss at the femoral neck, trochanter, and Ward's triangle was significantly associated with long-term PA (ANCOVA p &lt; .05), whereas no associations of bone loss and PA in lumbar spine were seen. PA is associated with a moderate rise in wrist fracture risk, which might be explained in part by a higher number of outdoor activities. Regular PA of at least 1½ hours per week does not seem to increase the risk of other fractures and might significantly decrease proximal femur bone loss among peri- and postmenopausal women. © 2010 American Society for Bone and Mineral Research.
A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: A randomized, placebo-controlled trial
Authors: Kawaguchi Hiroshi , Oka Hiroyuki , Jingushi Seiya , Izumi Toshihiro , Fukunaga Masao , Sato Katsumi , Matsushita Takashi , Nakamura Kozo ,   for the TESK Group
Published: June 2010

Abstract
Fibroblast growth factor 2 (FGF-2) is a potent mitogen for mesenchymal cells, and a local application of recombinant human FGF-2 (rhFGF-2) in a gelatin hydrogel has been reported to accelerate bone union in our animal studies and preparatory dose-escalation trial on patients with surgical osteotomy. We have performed a randomized, double-blind, placebo-controlled trial in which patients with fresh tibial shaft fractures of transverse or short oblique type were randomly assigned to three groups receiving a single injection of the gelatin hydrogel containing either placebo or 0.8 mg (low-dosage group) or 2.4 mg (high-dosage group) of rhFGF-2 into the fracture gap at the end of an intramedullary nailing surgery. Of 194 consecutive patients over 2 years, 85 met the eligibility criteria, and 70 (24 in the placebo group and 23 each in low- and high-dosage groups) completed the 24-week study. The cumulative percentages of patients with radiographic bone union were higher in the rhFGF-2-treated groups (p = .031 and .009 in low- and high-dosage group, respectively) compared with the placebo group, although there was no significant difference between low- and high-dosage groups (p = .776). At 24 weeks, 4, 1, and 0 patients in the placebo, low-dosage, and high-dosage groups, respectively, continued to show delayed union. No patient underwent a secondary intervention, and the time to full weight bearing without pain was not significantly different among the three groups (p = .567). There also was no significant difference in the profiles of adverse events among the groups. In conclusion, a local application of the rhFGF-2 hydrogel accelerated healing of tibial shaft fractures with a safety profile. © 2010 American Society for Bone and Mineral Research.
Mechanism of TNF‐α‐induced migration and hepatocyte growth factor production in human mesenchymal stem cells
Authors: Zhang Aibin , Wang Yan , Ye Zhou , Xie Haiyang , Zhou Lin , Zheng Shusen 
Published: June 2010

AbstractAccumulating evidence suggests that mesenchymal stem cells (MSCs) may decrease destructive inflammation and reduce tissue loss. Tumor necrosis factor‐α (TNF‐α) plays a central role in induction of proinflammatory signaling and paradoxically activates intracellular anti‐inflammatory survival pathways. In this study, we investigated whether TNF‐α could induce a chemotactic effect on human MSCs and stimulate their production of anti‐inflammatory factors in vitro, as well as determined mechanisms that mediated this effect. Migration assays demonstrated that TNF‐α had a chemotactic effect on MSCs. TNF‐α increased both hepatocyte growth factor (HGF) mRNA expression in MSCs and HGF secretion in conditioned medium. These effects were dependent on the p38 MAPK and PI3K/Akt, but not JNK and ERK signaling pathways. Furthermore, these effects were inhibited by a specific neutralizing antibody to TNF receptor II, but not TNF receptor I. We conclude that TNF‐α can enhance human MSCs migration and stimulate their production of HGF. These effects are mediated via a specific TNF receptor and signaling pathways. J. Cell. Biochem. 111: 469–475, 2010. © 2010 Wiley‐Liss, Inc.
LPA rescues ER stress‐associated apoptosis in hypoxia and serum deprivation‐stimulated mesenchymal stem cells
Authors: Li Zongwei , Wei Hua , Liu Xuebin , Hu Shengshou , Cong Xiangfeng , Chen Xi 
Published: June 2010

AbstractPoor viability of transplanted mesenchymal stem cells (MSCs) in the infracted heart has limited their therapeutic efficacy in cardiac repair after myocardial infarction. We previously demonstrated that hypoxia and serum deprivation (hypoxia/SD) induced mitochondria‐dependent apoptosis in MSCs, while lysophosphatidic acid (LPA) could almost completely block this apoptotic process. However, the role of endoplasmic reticulum (ER) stress and its upstream signaling events in hypoxia/SD‐induced MSC apoptosis remain largely unknown. Here we found that hypoxia/SD‐induced MSC apoptosis was associated with ER stress, as shown by the induction of CHOP expression and procaspase‐12 cleavage, while the effects were abrogated by LPA treatment, suggesting ER stress is also a target of LPA. Furthermore, hypoxia/SD induced p38 activation, inhibition of which resulted in decreases of apoptotic cells, procaspase‐12 cleavage and mitochondrial cytochrome c release that function in parallel in MSC apoptosis. Unexpectedly, p38 inhibition enhanced hypoxia/SD‐induced CHOP expression. Interestingly, p38 activation, a common process mediating various biological effects of LPA, was inhibited by LPA in this study, and the regulation of p38 pathway by LPA was dependent on LPA1/3/Gi/ERK1/2 pathway‐mediated MKP‐1 induction but independent of PI3K/Akt pathway. Collectively, our findings indicate that ER stress is a target of LPA to antagonize hypoxia/SD‐induced MSC apoptosis, and the modulation of mitochondrial and ER stress‐associated apoptotic pathways by LPA is at least partly dependent on LPA1/3/Gi/ERK/MKP‐1 pathway‐mediated p38 inhibition. This study may provide new anti‐apoptotic targets for elevating the viability of MSCs for therapeutic potential of cardiac repair. J. Cell. Biochem. 111: 811–820, 2010. © 2010 Wiley‐Liss, Inc.
Group parent training with immigrant chinese families: enhancing engagement and augmenting skills training
Authors: Lau Anna S. , Fung Joey J. , Yung Vanda 
Published: June 2010

AbstractParent training (PT) is an evidence‐based treatment for reducing and preventing child conduct problems and abusive parenting. However, questions have been raised about the dissemination of PT to culturally diverse families who hold different views on childrearing. Group PT was applied in two Chinese immigrant families illustrating strategies for addressing potential cultural barriers. The Incredible Years program builds in therapeutic process elements to address cultural concerns to enhance engagement. In addition, augmenting basic PT with additional skills training can help parents manage stressors common in immigrant families to facilitate uptake of new parenting skills. This implementation experience suggested that high‐risk immigrant Chinese parents can be effectively engaged in group PT, even when they are not in treatment voluntarily. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–15, 2010.
Evidence‐based practices with ethnic minorities: strange bedfellows no more
Authors: Morales Eduardo , Norcross John C. 
Published: June 2010

AbstractMulticulturalism and evidence‐based practice (EBP) in psychotherapy hailed from disparate sources and rarely interacted. These strange bedfellows have become fast friends in recent years as they recognize their crucial interdependence: multiculturalism without strong research risks becoming an empty political value and EBP without cultural sensitivity risks irrelevancy. In this article, the authors reviewed various incarnations and recent manifestations of their overdue intersection, including several conferences, federal initiatives, and organizational accomplishments. They introduced the subsequent 6 articles in this special issue of the Journal of Clinical Psychology: In Session, which described and illustrated cultural‐sensitive evidence‐based practices. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–9, 2010.
Carbonic anhydrase II regulates differentiation of ameloblasts via intracellular pH‐dependent JNK signaling pathway
Authors: Wang Xiaogu , Suzawa Tetsuo , Ohtsuka Hirotada , Zhao Baohong , Miyamoto Yoichi , Miyauchi Tomohiko , Nishimura Riko , Inoue Tomio , Nakamura Masanori , Baba Kazuyoshi , Kamijo Ryutaro 
Published: June 2010

AbstractDifferentiation of ameloblasts from undifferentiated epithelial cells is controlled by diverse growth factors, as well as interactions between epithelium and mesenchyme. However, there is a considerable lack of knowledge regarding the precise mechanisms that control ameloblast differentiation and enamel biomineralization. We found that the expression level of carbonic anhydrase II (CAII) is strongly up‐regulated in parallel with differentiation of enamel epithelium tissues, while the enzyme activity of CA was also increased along with differentiation in ameloblast primary cultures. The expression level of amelogenin, a marker of secretory‐stage ameloblasts, was enhanced by ethoxzolamide (EZA), a CA inhibitor, as well as CAII antisense (CAIIAS), whereas the expression of enamel matrix serine proteinase‐1 (EMSP‐1), a marker for maturation‐stage ameloblasts, was suppressed by both. These agents also promoted ameloblast proliferation. In addition, inhibition of ameloblast differentiation by EZA and CAIIAS was confirmed using tooth germ organ cultures. Furthermore, EZA and CAIIAS elevated intracellular pH in ameloblasts, while experimental decreases in intracellular pH abolished the effect of CAIIAS on ameloblasts and triggered the activation of c‐Jun N‐terminal kinase (JNK). SP600125, a JNK inhibitor, abrogated the response of ameloblasts to an experimental decrease in intracellular pH, while the inhibition of JNK also impaired ameloblast differentiation. These results suggest a novel role for CAII during amelogenesis, that is, controlling the differentiation of ameloblasts. Regulation of intracellular pH, followed by activation of the JNK signaling pathway, may be responsible for the effects of CAII on ameloblasts. J. Cell. Physiol. 225: 709–719, 2010. © 2010 Wiley‐Liss, Inc.
Shedding of microparticles by myofibroblasts as mediator of cellular cross‐talk during normal wound healing
Authors: Moulin Véronique J. , Mayrand Dominique , Messier Hugo , Martinez Maria Carmen , Lopez‐Vallé Carlos A. , Genest Hervé 
Published: June 2010

AbstractInteractions between cells are a crucial mechanism to correctly heal a wounded tissue. Myofibroblasts have a central role during healing but their means to communicate with other cells is unknown. Microparticles (MP) have demonstrated a potential role as mediators of cellular interactions during various diseases. We have analyzed the production of MP by normal (Wmyo) and pathological (hypertrophic scar, Hmyo) myofibroblasts and human dermal fibroblasts (Fb) when treated with serum or plasma as examples of body fluids. We have shown that the presence of these body fluids induced a very significant increase in MP production by Wmyo while no MP production was denoted for Hmyo and Fb. These effects were at least due to thermally sensitive protein(s) with a molecular mass >30 kDa. Furthermore, the increase in MP production was not linked to an increase in apoptotic Wmyo. MP characterization showed that VEGF and FGF2 were present in MP and that endothelial and (myo)fibroblast cell growth can be stimulated by MP treatment. We postulated that MP production by myofibroblasts could modulate mesenchymal cell growth and angiogenesis during normal healing. J. Cell. Physiol. 225: 734–740, 2010. © 2010 Wiley‐Liss, Inc.