bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clusterin is a potential molecular predictor for ovarian cancer patient's survival: targeting Clusterin improves response to paclitaxel
Authors: Hassan Mohamed K , Watari Hidemichi , Han Yimin , Mitamura Takashi , Hosaka Masayoshi , Wang Lei , Tanaka Shinya , Sakuragi Noriaki 
Published: December 2011

Abstract

Background
Clusterin is a cytoprotective chaperone protein involved in numerous physiological processes, carcinogenesis, tumor growth and tissue remodelling. The purpose of this study was to investigate whether clusterin (CLU), an antiapoptotic molecule, could be a potential predictor molecule for ovarian cancer and whether or not targeting this molecule can improve survival of ovarian cancer patients.

Methods
Clusterin expression was compared between ten primary and their recurrent tumors from same patients immunohistochemically. We analyzed prognostic significance of CLU expression in another 47 ovarian cancer tissue samples by immunohistochemistry. We used small interference RNA to knock down CLU in the chemo-resistant ovarian cancer cell lines. KF-TX and SKOV-3-TX, paclitaxel-resistant ovarian cancer cells, were established from parental KF and SKOV-3 chemo-sensitive cell lines, respectively. Either siRNA or second generation antisense oligodeoxynucleotide against CLU (OGX-011), which is currently evaluated in clinical phase II trials in other cancer s, was used to modulate sensitivity to paclitaxel (TX) in ovarian cancer cells in vitro. Cellular viability assay, FACS analysis and annexin V staining were used to evaluate the comparative effect of CLU knocking down in ovarian cancer cells.

Results
Immunohistochemical analysis of CLU expression in primary ovarian cancer tissue specimens and their recurrent counterparts from same patients demonstrated higher expression of CLU in the recurrent resistant tumors compared with their primary tumors. High expression of CLU by immunohistochemistry among 47 surgical tissue specimens of early-stage (stage I/II) ovarian cancer, who underwent complete cytoreduction as a primary surgery, significantly related to poor survival, while none of other clinicopathological factors analyzed were related to survival in this patient cohort. Secretory CLU (s-CLU; 60 KDa) expression was upregulated in TX-resistant ovarian cancer cells compared to parental cells. Transfection of siRNA or OGX-011 clearly reduced CLU expression. Cell viability assay, FACS analysis and annexin V staining demonstrated that targeting CLU expression by siRNA or OGX-011 sensitized ovarian cancer cells to TX.

Conclusion
We conclude that CLU could be a potential molecular target to predict survival while targeting this s-CLU may improve survival of patients with ovarian cancer.
Clinical and biomechanical outcome of minimal invasive and open repair of the Achilles tendon
Authors: Chan Alexander Pak-Hin , Chan Yue-Yan , Fong Daniel Tik-Pui , Wong Pamela Yuet-Kam , Lam Hoi-Yan , Lo Chun-Kwong , Yung Patrick Shu-Hang , Fung Kwai-Yau , Chan Kai-Ming 
Published: December 2011

Abstract

Introduction
With evolutions in surgical techniques, minimally invasive surgical (MIS) repair with Achillon applicator has been introduced. However, there is still a lack of literature to investigate into the clinical merits of MIS over open surgery. This study aims to investigate the correlation between clinical outcome, gait analysis and biomechanical properties comparing both surgical methods.

Materials and methods
A single centre retrospective review on all the consecutive operated patients between January 2004 and December 2008 was performed. Twenty-six patients (19 male and 7 female; age 40.4 ± 9.2 years) had experienced a complete Achilles tendon rupture with operative repair. Nineteen of the patients, 10 MIS versus 9 open repairs (13 men with a mean age of 40.54 ± 10.43 (range 23-62 yrs) and 6 women with a mean age of 45.33 ± 7.71 (range 35-57 yrs) were further invited to attend a thorough clinical assessment using Holz's scale and biomechanical evaluation at a mean of 25.3 months after operation. This study utilized the Cybex II isokinetic dynamometer to assess the isokinetic peak force of plantar-flexion and dorsiflexion of both ankles. The patients were also invited to return to our Gait Laboratory for analysis. The eight-infrared camera motion capture system (VICON, UK) was utilized for the acquisition of kinematic variables. Their anthropometric data was measured according to the Davis and coworkers' standard.

Results
The mean operative time and length of hospital stay were shorter in the MIS group. The operative time was 54.55 ± 15.15 minutes versus 68.80 ± 18.23 minutes of the MIS group and Open group respectively (p = 0.045), whereas length of stay was 3.36 ± 1.21 days versus 6.40 ± 3.70 days respectively (p = 0.039). There is statistically significant decrease (p = 0.005) in incision length in MIS group than the open surgery group, 3.23 ± 1.10 cm versus 9.64 ± 2.55 cm respectively. Both groups attained similar Holz's scores, 11.70 ± 0.95 versus 12.0 ± 1.50 respectively (p = 0.262). The mean percentage stance time of the injured leg for MIS patient was 58.44% while the mean percentage stance time of the injured leg for patients with open repair was 56.57%. T-test has shown there were no significance differences between the results of the two groups of patients. The loss of peak torque and total work done with respect to the injured side were similar between the MIS and open group.

Discussion and conclusion
MIS using Achillon method can achieve smaller incisions, shorter operative time and hospital stay. There is no statistical significance difference in clinical outcome, the stance time to strike time ratio and biomechanical properties on the leg receiving Achilles tendon repair using MIS method and open surgery.
Activation and maturation of peripheral blood T cells in HIV‐1‐infected and HIV‐1‐uninfected adults in Burkina Faso: a cross‐sectional study
Authors: Tiba Fabrice , Nauwelaers Frans , Sangaré Lassana , Coulibaly Boubacar , Kräusslich Hans‐Georg , Böhler Thomas 
Published: December 2011

BackgroundWe wanted to explore to what extent environmental exposure to immune stimulants, which is expected to be more present in rural than in urban settings, influences T cell activation and maturation in healthy and in HIV‐1‐infected individuals in Burkina Faso in west Africa.MethodsThe proportion of circulating naïve T cells and the expression of the T cell activation markers, CD95 and CD38, were analyzed by immunophenotyping and three‐colour flow cytometry in 63 healthy individuals and 137 treatment‐naïve HIV‐1‐infected subjects from Ouagadougou (urban setting) and 26 healthy adults and 61 treatment‐naïve patients from Nouna (rural).ResultsA slightly higher activation level of CD4+ and CD8+ peripheral blood T cells was seen in healthy adults living in Nouna than in those living in Ouagadougou. The percentages of naïve CD45RAbright CCR7+ T cells were not significantly different between both study sites. Taking into consideration that relatively more HIV‐1‐infected patients in Nouna were in an advanced disease stage, no relevant differences were seen in T cell activation and maturation between patients at both study sites. As expected, the percentage of CD95+ CD4+ and CD38+ CD8+ T cells and the respective antigen density on these cells was significantly higher in patients than in controls in both settings. The percentage of naïve CD8+ T cells was lower in HIV‐1‐infected subjects than in healthy controls irrespective of the study site, while a lower proportion of naïve CD4+ T cells in patients compared with controls was seen only in Nouna.ConclusionsEnvironmentally triggered immune activation may contribute to the increased expression of the activation markers CD95 and CD38 on peripheral blood T cells from healthy adults living in rural versus urban settings in Burkina Faso. T cell activation is further increased in HIV‐1‐infected individuals due to T cell loss and high plasma viral load levels. The observed variations in T cell activation levels or the proportion of naïve T cells in our study patients, however, are not explained by differences in CD4+ T cell counts or HIV‐1 plasma viral load levels alone.
Knowledge of HIV transmission and condom use among HIV‐positive heterosexual men and women in Guatemala
Authors: Delgado Hurtado Juan J , Pineda Marcela , Cazali Iris , Mejía Carlos 
Published: December 2011

BackgroundThe prevalence of HIV/AIDS in Guatemala among the general population is 0.79%, and 94% of transmission is directly related to sexual contact. Studies have been conducted on high‐ prevalence HIV‐positive populations (men who have sex with men, commercial sex workers and prisoners). Heterosexual transmission has gained importance in the epidemic in Central America. To our knowledge, no study addressing knowledge of mechanisms of HIV transmission and condom use has been done on HIV‐positive heterosexual men and women.MethodsA closed‐ended structured interview that addressed knowledge of mechanisms of HIV transmission and condom use was conducted on 283 heterosexual HIV‐positive men (54.8%) and women (45.2%) outpatients who attend the Roosevelt Hospital's Clinic of Infectious Diseases in Guatemala City. Differences between selected characteristics were examined for significance using the Chi‐square test. A multiple logistic regression was done to determine socio‐demographic variables associated with inconsistent condom use.ResultsOf the interviewed persons, 68.5% were either living with a partner or married, and 94.3% were currently using antiretroviral therapy. Most respondents knew the mechanisms of transmission of HIV. 81.7% and 87.3% reported always using a condom with their regular and casual sexual partner in the past year, respectively. There was no statistically difference in condom use according to the patient's formal education, gender, type of partner (regular or casual)or number of sexual partners. According to the interviewees, 72% of sexual partners in the past year were either HIV negative or of an unknown serostatus. Potentially, these HIV‐negative persons are at risk of contracting the virus. Among the main reasons given for not using a condom were: “my partner did not want to use a condom”; and “the condom irritates or makes my partner uncomfortable”.ConclusionsSince no socio‐demographic or sexual behavior variable was associated with inconsistent condom use, we recommend intensive and regular condom counselling for every heterosexual HIV‐positive outpatient who attends the clinic. Further studies should be done to determine condom use negotiation between partners; and to determine social, interpersonal and psychological factors that might affect the decision to use a condom or not.
Myxolipoma in the tongue - A clinical case report and review of the literature
Authors: Ono Shigehiro , Rana Majeed , Takechi Masaaki , Ogawa Ikuko , Okui Gaku , Mitani Yoshitsugu , Gellrich Nils-Claudius , Kamata Nobuyuki 
Published: December 2011

Abstract
In this article, we present our experience with a case of myxolipoma of the tongue.
Lipoma is a mesenchymal benign tumor occurring with relatively high frequency. However, myxolipoma, one of the histological variant of lipoma characterized by mature adipose tissue and abundant mucoid substances, in the oral cavity is quite rare.
The patient was a 52-year-old man who noticed a painless mass on the left border of tongue about 2 years ago. The lesion was noted at a complete medical checkup, and the patient was admitted to our institution for detailed examination. The mass was a palpable, soft and elastic nodule, 15 mm in diameter, covered with normal mucosa in the left inferior aspect of the tongue. The border of the tumor was well-defined, and computed tomography (CT) revealed a fat density within the mass. On the basis of these finding, the tumor was clinically diagnosed as lipoma and was excised under general anesthesia. Histopathologically, the tumor was a well-defined lobulated mass surrounded by a thin fibrous capsule within the muscle of the tongue. The tumor was diagnosed as myxolipoma because it was consisted of solid proliferation of mature adipocytes replaced by abundant mucoid substances. The post operative course was uneventful, and there was no evidence of recurrence 4 years after surgery.
Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
Authors: Ewald Ingrid P , Izetti Patrícia , Vargas Fernando R , Moreira Miguel AM , Moreira Aline S , Moreira-Filho Carlos A , Cunha Danielle R , Hamaguchi Sara , Camey Suzi A , Schmidt Aishameriane , Caleffi Maira , Koehler-Santos Patrícia , Giugliani Roberto , Ashton-Prolla Patricia 
Published: December 2011

Abstract
About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1 c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1 c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.
Marine pollution: Let us not forget beach sand
Authors: Galgani Francois , Ellerbrake Katrin , Fries Elke , Goreux Chantal 
Published: December 2011

Abstract

Background
Assessing the chemical or bacterial contamination in marine waters and sediments is a very common approach to evaluate marine pollution and associated risks. However, toxicity and organic pollution of beach sands have not yet been considered, except in adjacent waters. In the present study, the toxicity and the chemical contamination of natural beach sands collected 20 m from the shoreline at two sites located on the Mediterranean Sea (Marseille and La Marana, Corsica) were studied.

Results
Up to 16.93% (net percentage) abnormal or dead larvae was observed in elutriates prepared from the urban beach sand sample (Marseille); no significant toxicity was observed in the sample collected from the reference beach in La Marana. Results of Fourier transform infrared spectroscopy analyses revealed that no microplastics were present in either of the samples. Several polycyclic aromatic hydrocarbons [PAHs] in both samples and a larger number of individual PAHs in the urban sample than in the sample collected from the reference beach were detected. In addition, the antioxidant dioctyldiphenylamine was detected in both beach sand samples, whereby a higher concentration was found in La Marana than in Marseille. Calculated PAH concentrations in elutriates were generally higher than measured ones.

Conclusions
The results of this preliminary study provide evidence of toxicity and the presence of organic trace contaminants in beach sands from France. According to our results, monitoring using a combination of biotests and chemical analyses is recommended, especially of sediments from beaches abandoned to urban and industrial areas.
Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing
Authors: Harismendy Olivier , Schwab Richard B , Bao Lei , Olson Jeff , Rozenzhak Sophie , Kotsopoulos Steve K , Pond Stephanie , Crain Brian , Chee Mark S , Messer Karen , Link Darren R , Frazer Kelly A 
Published: December 2011

AbstractUltra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes. We present novel methods enhancing both laboratory workflow and mutation detection. We evaluate UDT-Seq true sensitivity and specificity (> 94% and > 99%, respectively) for low prevalence mutations in a mixing experiment and demonstrate its utility using six tumor samples. With an improved performance when run on the Illumina Miseq, the UDT-Seq assay is well suited for clinical applications to guide therapy and study clonal selection in heterogeneous samples.
Inhibition of NADPH oxidase activation by peptides mapping within the dehydrogenase region of Nox2-A “peptide walking” study
Authors: Dahan Iris , Molshanski-Mor Shahar , Pick Edgar 
Published: December 2011

ABSTRACT
In this study, the “peptide walking” approach was applied to the DH region of Nox2 (residues 288–570) with the purpose of identifying domains of functional importance in the assembly and/or catalytic function of the NADPH oxidase complex of phagocytes. Ninety-one overlapping 15-mer peptides were synthesized to cover the full length of the Nox2 DH region, and these were tested for the ability to interfere with the activation of the oxidase in vitro in two semirecombinant cell-free systems. The first consisted of phagocyte membranes p47phox, p67phox, and Rac1 and an amphiphile; the second was p47phox- and amphiphile-free and contained prenylated Rac1. We identified 10 clusters of inhibitory peptides with IC50 values of 10 μM, all of which were inhibitory, also in the absence of p47phox. Based on the identification of residues shared by peptides in a particular cluster, we defined 10 functional domains in the Nox2 DH region. One domain corresponded to one FAD-binding subdomain, and four domains overlapped parts of three NADPH-binding subdomains. As expected, most inhibitory peptides acted only when added prior to the completion of oxidase assembly, but peptides associated with two NADPH-binding subdomains were also active after assembly. Kinetic analysis demonstrated that inhibition by peptides was not explained by competition for substrates (FAD, NADPH) but was of a more complex nature: noncompetitive with respect to FAD and uncompetitive with respect to NADPH. We conclude that oxidase-inhibitory peptides, in five out of 10 clusters identified, act by interfering with FAD- and NADPH-related redox reactions.
Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer
Authors: Karlan Beth Y. , Oza Amit M. , Richardson Gary E. , Provencher Diane M. , Hansen Vincent L. , Buck Martin , Chambers Setsuko K. , Ghatage Prafull , Pippitt Charles H. , Brown John V. , Covens Allan , Nagarkar Raj V. , Davy Margaret , Leath Charles A. , Nguyen Hoa , Stepan Daniel E. , Weinreich David M. , Tassoudji Marjan , Sun Yu-Nien , Vergote Ignace B. 
Published: December 2011

Purpose To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2, plus weekly paclitaxel in patients with recurrent ovarian cancer. Patients and Methods Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg/m2 once weekly [QW], 3 weeks on/1 week off) plus intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics. Results One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade ≥ 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses. Conclusion AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.