bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer
Authors: Hong Yong Sang , Cho Hyeon Jin , Kim Sun Young , Jung Kyung Hae , Park Ji Won , Choi Hyo Seong , Oh Jae Hwan , Kim Byung Chang , Sohn Dae Kyung , Kim Dae Yong , Chang Hee Jin 
Published: July 2009

Abstract

Background
Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.

Methods
Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.

Results
The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.

Conclusion
Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.
Establishment and characterization of pleomorphic adenoma cell systems: an in-vitro demonstration of carcinomas arising secondarily from adenomas in the salivary gland
Authors: Maruyama Satoshi , Cheng Jun , Shingaki Susumu , Tamura Takashi , Asakawa Shuichi , Minoshima Shinsei , Shimizu Yoshiko , Shimizu Nobuyoshi , Saku Takashi 
Published: July 2009

Abstract

Background
Among the salivary gland carcinomas, carcinoma in pleomorphic adenoma has been regarded as a representative carcinoma type which arises secondarily in the background of a pre-existent benign pleomorphic adenoma. It is still poorly understood how and which benign pleomorphic adenoma cells transform into its malignant form, carcinoma ex pleomorphic adenoma.

Methods
We have established five cell systems from a benign pleomorphic adenoma of the parotid gland of a 61-year-old woman. They were characterized by immunofluorescence, classical cytogenetics, p53 gene mutational analysis, fluorescence in-situ hybridization, and histopathological and immunohistochemical examinations of their xenografts, to demonstrate their potency of secondary transformation.

Results
We established and characterized five cell systems (designated as SM-AP1 to SM-AP5) from a benign pleomorphic adenoma of the parotid gland. SM-AP1 to SM-AP3 showed polygonal cell shapes while SM-AP4 and SM-AP5 were spindle-shaped. SM-AP1-3 cells were immunopositive for keratin only, indicating their duct-epithelial or squamous cell differentiation, while SM-AP4/5 cells were positive for both keratin and S-100 protein, indicating their myoepithelial cell differentiation. Chromosome analyses showed numeral abnormalities such as 5n ploidies and various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9;13)(p13.3;q12.3) was shared by all five of the cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which resulted in generation of its nonsense gene product. Transplanted cells in nude mice formed subcutaneous tumors, which had histological features of squamous cell carcinoma with apparent keratinizing tendencies. In addition, they had ductal arrangements or plasmacytoid appearances of tumor cells and myxoid or hyaline stromata, indicating some characteristics of pleomorphic adenoma.

Conclusion
This study demonstrates in vitro that certain cell types from pleomorphic adenoma are able to clone and survive over a long term and develop subcutaneous tumors in nude mice. The histological features of squamous cell carcinoma from the transplanted cell systems in nude mice might suggest a secondary onset of malignancy from a pre-existing benign adenoma.
A qualitative study to assess school nurses' views on vaccinating 12–13 year old school girls against human papillomavirus without parental consent
Authors: Stretch Rebecca , McCann Rosemary , Roberts Stephen A , Elton Peter , Baxter David , Brabin Loretta 
Published: July 2009

Abstract

Background
In the UK, parental consent for the routine vaccination of 12–13 year olds schoolgirls against human papillomavirus (HPV) is recommended, although legally girls may be able to consent themselves. As part of a vaccine study conducted ahead of the National HPV Vaccine Programme we sought the views of school nurses on vaccinating girls who did not have parental consent.

Methods
HPV vaccination was offered to all 12 year old girls attending schools in two Primary Care Trusts in Greater Manchester. At the end of the study semi-structured, tape-recorded interviews were conducted with school nurses who had delivered the vaccine (Cervarix™). The interview template was based on concepts derived from the Theory of Planned Behaviour. Transcripts were analysed thematically in order to understand school nurses' intentions to implement vaccination based on an assessment of Gillick competency.

Results
School nurses knew how to assess the competency of under-16s but were still unwilling to vaccinate if parents had refused permission. If parents had not returned the consent form, school nurses were willing to contact parents, and also to negotiate with parents who had refused consent. They seemed unaware that parental involvement required the child's consent to avoid breaking confidentiality. Nurses' attitudes were influenced by the young appearance and age of the school year group rather than an individual's level of maturity. They were also confused about the legal guidelines governing consent. School nurses acknowledged the child's right to vaccination and strongly supported prevention of HPV infection but ultimately believed that it was the parents' right to give consent. Most were themselves parents and shared other parents' concerns about the vaccine's novelty and unknown long-term side effects. Rather than vaccinate without parental consent, school nurses would defer vaccination.

Conclusion
Health providers have a duty of care to girls for whom no parental consent for HPV vaccination has been given, and in the UK, this includes conducting, and acting upon, an assessment of the maturity and competence of an adolescent minor. To facilitate this, policies, training and support structures for health providers should be implemented.
Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester
Authors: Reulen Sanne WA , van Baal Ingrid , Raats Jos MH , Merkx Maarten 
Published: July 2009

Abstract

Background
Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging.

Results
Targeting to the periplasm of E. coli allowed efficient production of correctly-folded single-domain antibody (sdAb)-intein fusions proteins. On column purification and 2-mercapthoethanesulfonic acid (MESNA)-induced cleavage yielded single-domain antibodies with a reactive C-terminal MESNA thioester in good yields. These thioester-functionalized single-domain antibodies allowed synthesis of immunomicelles via native chemical ligation in a single step.

Conclusion
A novel procedure was developed to obtain soluble, well-folded single-domain antibodies with reactive C-terminal thioesters in good yields. These proteins are promising building blocks for the chemoselective functionalization via NCL of a broad range of nanoparticle scaffolds, including micelles, liposomes and dendrimers.
A novel bacterial isolate Stenotrophomonas maltophilia as living factory for synthesis of gold nanoparticles
Authors: Nangia Yogesh , Wangoo Nishima , Goyal Nisha , Shekhawat G , Suri C Raman 
Published: July 2009

Abstract

Background
The synthesis of gold nanoparticles (GNPs) has received considerable attention with their potential applications in various life sciences related applications. Recently, there has been tremendous excitement in the study of nanoparticles synthesis by using some natural biological system, which has led to the development of various biomimetic approaches for the growth of advanced nanomaterials. In the present study, we have demonstrated the synthesis of gold nanoparticles by a novel bacterial strain isolated from a site near the famous gold mines in India. A promising mechanism for the biosynthesis of GNPs by this strain and their stabilization via charge capping was investigated.

Results
A bacterial isolate capable of gold nanoparticle synthesis was isolated and identified as a novel strain of Stenotrophomonas malophilia (AuRed02) based on its morphology and an analysis of its 16S rDNA gene sequence. After 8 hrs of incubation, monodisperse preparation of gold nanoparticles was obtained. Gold nanoparticles were characterized and found to be of ~40 nm size. Electrophoresis, Zeta potential and FTIR measurements confirmed that the particles are capped with negatively charged phosphate groups from NADP rendering them stable in aqueous medium.

Conclusion
The process of synthesis of well-dispersed nanoparticles using a novel microorganism isolated from the gold enriched soil sample has been reported in this study, leading to the development of an easy bioprocess for synthesis of GNPs. This is the first study in which an extensive characterization of the indigenous bacterium isolated from the actual gold enriched soil was conducted. Promising mechanism for the biosynthesis of GNPs by the strain and their stabilization via charge capping is suggested, which involves an NADPH-dependent reductase enzyme that reduces Au3+ to Au0 through electron shuttle enzymatic metal reduction process.
Changes in smoking prevalence among first- and second-generation Turkish migrants in Germany – an analysis of the 2005 Microcensus
Authors: Reeske Anna , Spallek Jacob , Razum Oliver 
Published: July 2009

Abstract

Background
Compared to the majority population of a host country, migrants tend to have different health risks and health behaviour. We have hypothesised that these differences diminish with time passed since migration. We tested this hypothesis by examining smoking behaviour among Turkish migrants and their children born in Germany (second-generation migrants), stratified by educational level and, for the first generation, length of residence.

Methods
We estimated the prevalence of smoking based on the representative 2005 Mikrozensus, an annual survey including 1% of Germany's households. The 2005 Microcensus was the first to provide information that makes it possible to differentiate between first- and second-generation Turkish migrants. In total, 12,288 Turkish migrants and 421,635 native-born Germans were included in our study. The unit non-response is generally low (about 6% in 2005) because participation in the Microcensus is obligatory.

Results
We found the prevalence of smoking in second-generation male Turkish migrants to be lower than in the first-generation group: 47.0% of first-generation Turkish migrants with a high level of education were smokers, in contrast to only 37.6% in the second generation. Within the German reference population, 29.9% were smokers. The percentage of Turkish women in our sample who smoked was generally smaller, but was not significantly lower in the second generation. In fact, the prevalence of smoking was highest among Turkish women of the second generation with a low level of education (40.9%), similar to younger second-generation German women with the same level of education.

Conclusion
We present the first representative data on changes in the prevalence of a risk factor for many chronic diseases among Turkish migrants in Germany. Male Turkish migrants (with a high level of education) showed a decrease over the generations while smoking prevalences of female Turkish migrants increased. In the second generation, prevalences partly converged with those of the German reference population or were even higher. Our hypothesis – that migration can be interpreted as a "health transition" – was thus partly confirmed.
Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b
Authors: Samalecos Annemarie , Reimann Katja , Wittmann Stefanie , Schulte Heinrich M , Brosens Jan J , Bamberger Ana-Maria , Gellersen Birgit 
Published: July 2009

Abstract

Background
Coordinated differentiation of the endometrial compartments in the second half of the menstrual cycle is a prerequisite for the establishment of pregnancy. Endometrial stromal cells (ESC) decidualize under the influence of ovarian progesterone to accommodate implantation of the blastocyst and support establishment of the placenta. Studies into the mechanisms of decidualization are often hampered by the lack of primary ESC. Here we describe a novel immortalized human ESC line.

Methods
Primary ESC were immortalized by the transduction of telomerase. The resultant cell line, termed St-T1b, was characterized for its morphological and biochemical properties by immunocytochemistry, RT-PCR and immunoblotting. Its progestational response was tested using progesterone and medroxyprogesterone acetate with and without 8-Br-cAMP, an established inducer of decidualization in vitro.

Results
St-T1b were positive for the fibroblast markers vimentin and CD90 and negative for the epithelial marker cytokeratin-7. They acquired a decidual phenotype indistinguishable from primary ESC in response to cAMP stimulation. The decidual response was characterized by transcriptional activation of marker genes, such as PRL, IGFBP1, and FOXO1, and enhanced protein levels of the tumor suppressor p53 and the metastasis suppressor KAI1 (CD82). Progestins alone had no effect on St-T1b cells, but medroxyprogesterone acetate greatly enhanced the cAMP-stimulated expression of IGFBP-1 after 3 and 7 days. Progesterone, albeit more weakly, also augmented the cAMP-induced IGFBP-1 production but only after 7 days of treatment. The cell line remained stable in continuous culture for more than 150 passages.

Conclusion
St-T1b express the appropriate phenotypic ESC markers and their decidual response closely mimics that of primary cultures. Decidualization is efficiently induced by cAMP analog and enhanced by medroxyprogesterone acetate, and, to a lesser extent, by natural progesterone. St-T1b cells therefore serve as a useful model for primary ESC.
KSP inhibitor ARRY-520 as a substitute for Paclitaxel in Type I ovarian cancer cells
Authors: Kim Ki Hyung , Xie Yanhua , Tytler Ewan M , Woessner Richard , Mor Gil , Alvero Ayesha B 
Published: July 2009

AbstractBackgroundWe previously described a sub-population of epithelial ovarian cancer (EOC) cells with a functional TLR-4/MyD88/NF-κB pathway (Type I EOC cells), which confers the capacity to respond to Paclitaxel, a known TLR-4 ligand, by enhancing NF-κB activity and upregulating cytokine secretion – events that are known to promote tumor progression. It is therefore important to distinguish those patients that should not receive Paclitaxel; it is also important to identify alternative chemotherapy options that would benefit this sub-group of patients. The objective of this study is to determine if the KSP inhibitor, ARRY-520, can be a substitute for Paclitaxel in patients with Type I EOC.MethodsEOC cells isolated from either ascites or tumor tissue were treated with increasing concentrations of ARRY-520 or Paclitaxel and cell viability determined. Activation of the apoptotic pathway was determined using Western blot analysis. Mitochondrial integrity was quantified using JC1 dye. Cytokine profiling was performed from supernatants using xMAP technology. NF-κB activity was measured using a Luciferase reporter system.In vivoactivity was determined using a subcutaneous xenograft mouse model.ResultsARRY-520 and Paclitaxel exhibited the same cytotoxic effect on Type I and II cells. The GI50at 48 h for Type II EOC cells was 0.0015 μM and 0.2 μM for ARRY-520 and Paclitaxel, respectively. For Type I EOC cells, the GI50at 48 h was > 3 μM and >20 μM for ARRY-520 and Paclitaxel, respectively. Decrease in the number of viable cells was accompanied by mitochondrial depolarization and caspase activation. Unlike Paclitaxel, ARRY-520 did not induce NF-κB activation, did not enhance cytokine secretion, nor induce ERK phosphorylation in Type I EOC cells.ConclusionAdministration of Paclitaxel to patients with high percentage Type I cancer cells could have detrimental effects due to Paclitaxel-induced enhancement of NF-κB and ERK activities, and cytokine production (e.g. IL-6), which promote chemoresistance and tumor progression. ARRY-520 has similar anti-tumor activity in EOC cells as that of Paclitaxel. However, unlike Paclitaxel, it does not induce these pro-tumor effects in Type I cells. Therefore, the KSP inhibitor ARRY-520 may represent an alternative to Paclitaxel in this subgroup of EOC patients.
A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre
Authors: Navarro Pablo , Chantalat Sophie , Foglio Mario , Chureau Corinne , Vigneau Sébastien , Clerc Philippe , Avner Philip , Rougeulle Claire 
Published: July 2009

AbstractBackgroundDelimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (Xic), theXistlocus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).ResultsWe describe here that developmentally regulated transcription ofTsix, a crucial non-coding antisense toXist, is required to block the spreading of the H3K27me3 domain to the adjacent H3K4me2-richXistregion. Analyses of a series of distinctTsixmutations suggest that the underlying mechanism involves the RNA Polymerase II accumulating at theTsix3'-end. Furthermore, we report additional unexpected long-range effects ofTsixon the distal sub-region of theXic, involved inXic-Xictrans-interactions.ConclusionThese data point toward a role for transcription of non-coding RNAs as a developmental strategy for the establishment of functionally distinct domains within the mammalian genome.
Colorectal Cancer Risk Perception on the Basis of Genetic Test Results in Individuals at Risk for Lynch Syndrome
Authors: Grover Shilpa , Stoffel Elena M. , Mercado Rowena C. , Ford Beth M. , Kohlman Wendy K. , Shannon Kristen M. , Conrad Peggy G. , Blanco Amie M. , Terdiman Jonathan P. , Gruber Stephen B. , Chung Daniel C. , Syngal Sapna 
Published: July 2009

Purpose Lynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. Patients and Methods A total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. Results Of the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as “high” or “very high” compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome–associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. Conclusion Patients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.
Risk-Stratified Therapy and the Intensive Use of Cytarabine Improves the Outcome in Childhood Acute Myeloid Leukemia: The AML99 Trial From the Japanese Childhood AML Cooperative Study Group
Authors: Tsukimoto Ichiro , Tawa Akio , Horibe Keizo , Tabuchi Ken , Kigasawa Hisato , Tsuchida Masahiro , Yabe Hiromasa , Nakayama Hideki , Kudo Kazuko , Kobayashi Ryoji , Hamamoto Kazuko , Imaizumi Masue , Morimoto Akira , Tsuchiya Shigeru , Hanada Ryoji 
Published: July 2009

Purpose To improve the prognosis in children with newly diagnosed acute myeloid leukemia (AML) by introducing a dose-dense intensive chemotherapy regimen and an appropriate risk stratification system. Patients and Methods Two hundred forty children with de novo AML were treated with continuous cytarabine-based induction therapy and stratified to three risk groups based on the initial treatment response, age, and WBC at diagnosis and cytogenetics. All of the patients were treated with intensive consolidation chemotherapy including three or four courses of high-dose cytarabine. Allogeneic hematopoietic stem-cell transplantation (HSCT) was indicated for only the intermediate-risk patients with matched related donors and for all the high-risk subsets. Results Two hundred twenty-seven children (94.6%) achieved a complete remission (CR). Four children demonstrated induction death. The median follow-up of the live patients was 55 months (range, 37 to 73 months). The 5-year overall survival of all 240 children was 75.6% (95% CI, 70.3% to 81.4%) and event-free survival was 61.6% (95% CI, 55.8% to 68.1%). The 5-year disease-free survival in each risk group were 71.3% (95% CI, 63.4% to 80.2%) in the low-risk group (n = 112), 59.8% (95% CI, 50.6% to 70.7%) in the intermediate-risk group (n = 92), and 56.5% (95% CI, 39.5% to 80.9%) in the high-risk group (n = 23). Eight children died during the first CR, including four after HSCT. Conclusion A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.