99 research outputs found

    Females with paired occurrence of cancers in the UADT and genital region have a higher frequency of either Glutathione S-transferase M1/T1 null genotype

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    Upper Aero digestive Tract (UADT) is the commonest site for the development of second cancer in females after primary cervical cancer. Glutathione S-transferase (GSTM1 and / or T1) null genotype modulates the risk of developing UADT cancer (primary as well as second cancer). The aim of this study was to evaluate the difference in GST null genotype frequencies in females with paired cancers in the UADT and genital region as compared to females with paired cancers in the UADT and non-genital region. Forty-nine females with a cancer in the UADT and another cancer (at all sites-genital and non-genital) were identified from a database of patients with multiple primary neoplasms and were analyzed for the GSTM1 and T1 genotype in addition to known factors such as age, tobacco habits, alcohol habits and family history of cancer. Frequencies of GSTM1 null, GSTT1 null, and either GSTM1/T1 null were higher in females with paired occurrence of cancer in the UADT and genital site (54%, 33% and 75% respectively) in comparison to females with paired occurrence of cancer in the UADT and non-genital sites (22%, 6% and 24% respectively). The significantly higher inherited frequency of either GSTM1/T1 null genotype in females with a paired occurrence of cancers in UADT and genital region (p = 0.01), suggests that these females are more susceptible to damage by carcinogens as compared to females who have UADT cancers in association with cancers at non-genital sites

    Coarsening and Pinning in the Self-consistent Solution of Polymer Blends Phase-Separation Kinetics

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    We study analytically a continuum model for phase-separation in binary polymer blends based on the Flory-Huggins-De Gennes free energy, by means of the self-consistent large-nn limit approach. The model is solved for values of the parameters corresponding to the weak and strong segregation limits. For deep quenches we identify a complex structure of intermediate regimes and crossovers characterized by the existence of a time domain such that phase separation is pinned, followed by a preasymptotic regime which in the scalar case corresponds to surface diffusion. The duration of the pinning is analytically computed and diverges in the strong segregation limit. Eventually a late stage dynamics sets in, described by scaling laws and exponents analogous to those of the corresponding small molecule systems.Comment: 16 pages, 5 figures. Submitted to Phys. Rev.

    Spinodal Decomposition in a Binary Polymer Mixture: Dynamic Self Consistent Field Theory and Monte Carlo Simulations

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    We investigate how the dynamics of a single chain influences the kinetics of early stage phase separation in a symmetric binary polymer mixture. We consider quenches from the disordered phase into the region of spinodal instability. On a mean field level we approach this problem with two methods: a dynamical extension of the self consistent field theory for Gaussian chains, with the density variables evolving in time, and the method of the external potential dynamics where the effective external fields are propagated in time. Different wave vector dependencies of the kinetic coefficient are taken into account. These early stages of spinodal decomposition are also studied through Monte Carlo simulations employing the bond fluctuation model that maps the chains -- in our case with 64 effective segments -- on a coarse grained lattice. The results obtained through self consistent field calculations and Monte Carlo simulations can be compared because the time, length, and temperature scales are mapped onto each other through the diffusion constant, the chain extension, and the energy of mixing. The quantitative comparison of the relaxation rate of the global structure factor shows that a kinetic coefficient according to the Rouse model gives a much better agreement than a local, i.e. wave vector independent, kinetic factor. Including fluctuations in the self consistent field calculations leads to a shorter time span of spinodal behaviour and a reduction of the relaxation rate for smaller wave vectors and prevents the relaxation rate from becoming negative for larger values of the wave vector. This is also in agreement with the simulation results.Comment: Phys.Rev.E in prin

    Use of a trabecular metal implant in ankle arthrodesis after failed total ankle replacement: A short-term follow-up of 13 patients

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    Patients and methods 13 patients with a migrated or loose total ankle implant underwent arthrodesis with the use of a retrograde intramedullary nail through a trabecular metal Tibial Cone. The mean follow-up time was 1.4 (0.6-3.4) years. Results At the last examination, 7 patients were pain-free, while 5 had some residual pain but were satisfied with the procedure. 1 patient was dissatisfied and experienced pain and swelling when walking. The implant-bone interfaces showed no radiographic zones or gaps in any patient, indicating union. Interpretation The method is a new way of simplifying and overcoming some of the problems of performing arthrodesis after failed total ankle replacement

    Multiple Pathway-Based Genetic Variations Associated with Tobacco Related Multiple Primary Neoplasms

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    BACKGROUND: In order to elucidate a combination of genetic alterations that drive tobacco carcinogenesis we have explored a unique model system and analytical method for an unbiased qualitative and quantitative assessment of gene-gene and gene-environment interactions. The objective of this case control study was to assess genetic predisposition in a biologically enriched clinical model system of tobacco related cancers (TRC), occurring as Multiple Primary Neoplasms (MPN). METHODS: Genotyping of 21 candidate Single Nucleotide Polymorphisms (SNP) from major metabolic pathways was performed in a cohort of 151 MPN cases and 210 cancer-free controls. Statistical analysis using logistic regression and Multifactor Dimensionality Reduction (MDR) analysis was performed for studying higher order interactions among various SNPs and tobacco habit. RESULTS: Increased risk association was observed for patients with at least one TRC in the upper aero digestive tract (UADT) for variations in SULT1A1 Arg²¹³His, mEH Tyr¹¹³His, hOGG1 Ser³²⁶Cys, XRCC1 Arg²⁸⁰His and BRCA2 Asn³⁷²His. Gene-environment interactions were assessed using MDR analysis. The overall best model by MDR was tobacco habit/p53(Arg/Arg)/XRCC1(Arg³⁹⁹His)/mEH(Tyr¹¹³His) that had highest Cross Validation Consistency (8.3) and test accuracy (0.69). This model also showed significant association using logistic regression analysis. CONCLUSION: This is the first Indian study on a multipathway based approach to study genetic susceptibility to cancer in tobacco associated MPN. This approach could assist in planning additional studies for comprehensive understanding of tobacco carcinogenesis

    Pseudolumen Size and Perimeter in Prostate Cancer: Correlation with Patient Outcome

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    We demonstrated in 2011 that 61% of men with postoperative PSA failure had some cribriform pattern of prostate cancer, versus 16% of nonfailures (OR = 5.89, P < .0001). That study used digitized radical prostatectomy slides from 153 men, 76 failures (≥0.2 ng/mL) matched to 77 nonfailures. The current study's hypothesis: pseudolumen size and shape variability could stratify outcome within histologic patterns (single separate acini, separate acini with undulating lumens, fused small acini, papillary, cribriform). Pseudolumens were filled digitally on image captures from previously annotated specimens. Among all 5 patterns, pseudolumen spaces averaged smaller in failures than nonfailures. After multivariate analysis controlling for stage, age, margin, cancer amount, prostate volume, and presence of individual cells (grade 5), this retained significance only for the undulating-lumens and papillary patterns. In undulating-lumens pattern, PSA failures had smaller mean pseudolumen space sizes (P = .03) but larger perimeters (P = .04), implying more pseudolumen irregularity. In papillary pattern, the number of pseudolumen spaces was higher in failures (P = .015), space size was smaller (P = .11), perimeters were smaller (P = .04), and perimeter/size ratio was higher (P = .02). In conclusion, digitally measured pseudolumen size and shape may associate with outcome

    P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

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    Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues
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