bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians
Authors: Prasad Pushplata , Tiwari Arun K , Kumar KM Prasanna , Ammini AC , Gupta Arvind , Gupta Rajeev , Thelma BK 
Published: May 2007

Abstract

Background
Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI). Transforming growth factor β1 (TGF β1) induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα), chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR)-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs) from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency.

Methods
Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl) constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR) and 95% confidence intervals (CI). Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed.

Results
SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency <0.05) and therefore were not considered for case-control analysis. A significant allelic association of 59029G>A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84). In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035).

Conclusion
Of the various cytokine gene polymorphisms tested, allele 59029A of CCR5 gene is significantly associated with diabetic renal insufficiency among Asian Indians. Result obtained for 59029G>A SNP of CCR5 gene is in conformity with reports from a Japanese population but due to sub-optimal power of the sample, replication in larger sample set is warranted.
Theory of obstetrics: An epidemiologic framework for justifying medically indicated early delivery
Authors: Joseph K S 
Published: May 2007

AbstractBackgroundModern obstetrics is faced with a serious paradox. Obstetric practice is becoming increasingly interventionist based on empirical evidence but without a theoretical basis for such intervention. Whereas obstetric models of perinatal death show that mortality declines exponentially with increasing gestational duration, temporal increases in medically indicated labour induction and cesarean delivery have resulted in rising rates of preterm birth and declining rates of postterm birth. Other problems include a disconnection between patterns of gestational age-specific growth restriction (constant across gestation) and gestational age-specific perinatal mortality (exponential decline with increasing duration) and the paradox of intersecting perinatal mortality curves (low birth weight infants of smokers have lower neonatal mortality rates than the low birth weight infants of non-smokers).DiscussionThe fetuses at risk approach is a causal model that brings coherence to the various perinatal phenomena. Under this formulation, pregnancy complications (such as preeclampsia), labour induction/cesarean delivery, birth, revealed small-for-gestational age and death show coherent patterns of incidence. The fetuses at risk formulation also provides a theoretical justification for medically indicated early delivery, the cornerstone of modern obstetrics. It permits a conceptualization of the number needed to treat (e.g., as low as 2 for emergency cesarean delivery in preventing perinatal death given placental abruption and fetal bradycardia) and a calculation of the marginal number needed to treat (i.e., the number of additional medically indicated labour inductions/cesarean deliveries required to prevent one perinatal death). Data from the United States showed that between 1995–96 and 1999–2000 rates of labour induction/cesarean delivery increased by 45.1 per 1,000 and perinatal mortality decreased by 0.31 per 1,000 total births among singleton pregnancies at > = 28 weeks of gestation. The marginal number needed to treat was 145 (45.1/0.31), showing that 145 excess labour inductions/cesarean deliveries in 1999–2000 (relative to 1995–96) were responsible for preventing 1 perinatal death among singleton pregnancies at > = 28 weeks gestation.SummaryThe fetuses at risk approach, with its focus on incidence measures, provides a coherent view of perinatal phenomena. It also provides a theoretical justification for medically indicated early delivery and reconciles the contemporary divide between obstetric theory and obstetric practice.
Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo
Authors: Klenke Frank M , Abdollahi Amir , Bertl Elisabeth , Gebhard Martha-Maria , Ewerbeck Volker , Huber Peter E , Sckell Axel 
Published: May 2007

Abstract

Background
As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo.

Methods
In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy.

Results
SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings.

Conclusion
SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1. The experimental data obtained provide rationale to further develop the strategy of the use of the angiogenesis inhibitor SU6668 in the treatment of chondrosarcomas in addition to established therapies such as surgery.
Silencing of the XAF1 gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-β
Authors: Micali O Cristina , Cheung Herman H , Plenchette Stéphanie , Hurley Sandra L , Liston Peter , LaCasse Eric C , Korneluk Robert G 
Published: May 2007

Abstract

Background
XIAP-associated factor 1 (XAF1) is a putative tumor suppressor that exerts its proapoptotic effects through both caspase-dependent and – independent means. Loss of XAF1 expression through promoter methylation has been implicated in the process of tumorigenesis in a variety of cancers. In this report, we investigated the role of basal xaf1 promoter methylation in xaf1 expression and assessed the responsiveness of cancer cell lines to XAF1 induction by IFN-β.

Methods
We used the conventional bisulfite DNA modification and sequencing method to determine the methylation status in the CpG sites of xaf1 promoter in glioblastoma (SF539, SF295), neuroblastoma (SK-N-AS) and cervical carcinoma (HeLa) cells. We analysed the status and incidence of basal xaf1 promoter methylation in xaf1 expression in non-treated cells as well as under a short or long exposure to IFN-β. Stable XAF1 glioblastoma knock-down cell lines were established to characterize the direct implication of XAF1 in IFN-β-mediated sensitization to TRAIL-induced cell death.

Results
We found a strong variability in xaf1 promoter methylation profile and responsiveness to IFN-β across the four cancer cell lines studied. At the basal level, aberrant promoter methylation was linked to xaf1 gene silencing. After a short exposure, the IFN-β-mediated reactivation of xaf1 gene expression was related to the degree of basal promoter methylation. However, in spite of continued promoter hypermethylation, we find that IFN-β induced a transient xaf1 expression, that in turn, was followed by promoter demethylation upon a prolonged exposure. Importantly, we demonstrated for the first time that IFN-β-mediated reactivation of endogenous XAF1 plays a critical role in TRAIL-induced cell death since XAF1 knock-down cell lines completely lost their IFN-β-mediated TRAIL sensitivity.

Conclusion
Together, these results suggest that promoter demethylation is not the sole factor determining xaf1 gene induction under IFN-β treatment. Furthermore, our study provides evidence that XAF1 is a crucial interferon-stimulated gene (ISG) mediator of IFN-induced sensitization to TRAIL in cancer.
Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis
Authors: Turashvili Gulisa , Bouchal Jan , Baumforth Karl , Wei Wenbin , Dziechciarkova Marta , Ehrmann Jiri , Klein Jiri , Fridman Eduard , Skarda Jozef , Srovnal Josef , Hajduch Marian , Murray Paul , Kolar Zdenek 
Published: May 2007

Abstract

Background
Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells.

Methods
We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR.

Results
Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC.

Conclusion
IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.
Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks
Authors: Fensterer Heiko , Radlwimmer Bernhard , Sträter Jörn , Buchholz Malte , Aust Daniela E , Julié Catherine , Radvanyi François , Nordlinger Bernard , Belluco Claudio , Van Cutsem Eric , Köhne Claus-Henning , Kestler Hans A , Schwaenen Carsten , Nessling Michelle , Lutz Manfred P , Lichter Peter , Gress Thomas M ,   the EORTC Gastrointestinal (GI) Group
Published: May 2007

AbstractBackgroundThe identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.MethodsTo verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.ResultsThe majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.ConclusionArchival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.
Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer
Authors: Zhou Yamei , Yau Christina , Gray Joe W , Chew Karen , Dairkee Shanaz H , Moore Dan H , Eppenberger Urs , Eppenberger-Castori Serenella , Benz Christopher C 
Published: May 2007

Abstract

Background
Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen.

Methods
Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA) or the proteasome inhibitor bortezomib (PS341), alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108), each having different patient age and adjuvant tamoxifen treatment characteristics.

Results
Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases (UCSF, Rotterdam, Amsterdam, Basel), high expression of all three NFκB and AP-1 upregulated genes was associated with earliest metastatic relapse.

Conclusion
Altogether, these findings implicate increased NFκB and AP-1 transcriptional responses with tamoxifen resistant breast cancer and early metastatic relapse, especially in younger patients. These findings also suggest that agents capable of preventing NFκB and AP-1 gene activation may prove useful in restoring the endocrine responsiveness of such high-risk ER-positive breast cancers.
Potential cost savings with terrestrial rabies control
Authors: Recuenco Sergio , Cherry Bryan , Eidson Millicent 
Published: May 2007

AbstractBackgroundThe cost-benefit of raccoon rabies control strategies such as oral rabies vaccination (ORV) are under evaluation. As an initial quantification of the potential cost savings for a control program, the collection of selected rabies cost data was pilot tested for five counties in New York State (NYS) in a three-year period.MethodsRabies costs reported to NYS from the study counties were computerized and linked to a human rabies exposure database. Consolidated costs by county and year were averaged and compared.ResultsReported rabies-associated costs for all rabies variants totalled $2.1 million, for human rabies postexposure prophylaxes (PEP) (90.9%), animal specimen preparation/shipment to laboratory (4.7%), and pet vaccination clinics (4.4%). The proportion that may be attributed to raccoon rabies control was 37% ($784,529). Average costs associated with the raccoon variant varied across counties from $440 to $1,885 per PEP, $14 to $44 per specimen, and $0.33 to $15 per pet vaccinated.ConclusionRabies costs vary widely by county in New York State, and were associated with human population size and methods used by counties to estimate costs. Rabies cost variability must be considered in developing estimates of possible ORV-related cost savings. Costs of PEPs and specimen preparation/shipments, as well as the costs of pet vaccination provided by this study may be valuable for development of more realistic scenarios in economic modelling of ORV costs versus benefits.
Acute hepatitis C virus infection assessment among chronic hemodialysis patients in the Southwest Parana State, Brazil
Authors: Engel Maricea , Malta Fernanda M , Gomes Michele MS , Mello Isabel MVGC , Pinho João RR , Ono-Nita Suzane K , Carrilho Flair J 
Published: May 2007

Abstract

Background
Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C.

Methods
Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C.

Results
During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated.

Conclusion
Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004.
AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study
Authors: Thomas Michael , Sheran Jane , Smith Natalie , Fonseca Sofia , Lee Amanda J 
Published: May 2007

Abstract

Background
Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma.

Methods
We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means.

Results
No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8).
Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15.
Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant adverse events were noted.

Conclusion
AKL1 treatment was well tolerated. No significant improvements in lung function, symptoms, or quality of life were seen, although consistent trends were seen to improvements in patient-centered outcomes. Further studies are needed.