Identification and validation of genes involved in gastric tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is one of the common cancers seen in south India. Unfortunately more than 90% are advanced by the time they report to a tertiary centre in the country. There is an urgent need to characterize these cancers and try to identify potential biomarkers and novel therapeutic targets.</p> <p>Materials and methods</p> <p>We used 24 gastric cancers, 20 Paired normal (PN) and 5 apparently normal gastric tissues obtained from patients with non-gastric cancers (Apparently normal - AN) for the microarray study followed by validation of the significant genes (n = 63) by relative quantitation using Taqman Low Density Array Real Time PCR. We then used a custom made Quantibody protein array to validate the expression of 15 proteins in gastric tissues (4 AN, 9 PN and 9 gastric cancers). The same array format was used to study the plasma levels of these proteins in 58 patients with gastric cancers and 18 from patients with normal/non-malignant gastric conditions.</p> <p>Results</p> <p>Seventeen genes (ASPN, CCL15/MIP-1δ, MMP3, SPON2, PRSS2, CCL3, TMEPAI/PMEPAI, SIX3, MFNG, SOSTDC1, SGNE1, SST, IGHA1, AKR1B10, FCGBP, ATP4B, NCAPH2) were shown to be differentially expressed between the tumours and the paired normal, for the first time. EpCAM (p = 0.0001), IL8 (p = 0.0003), CCL4/MIP-1β (p = 0.0026), CCL20/MIP-3α (p = 0.039) and TIMP1 (p = 0.0017) tissue protein levels were significantly different (Mann Whitney U test) between tumours versus AN & PN. In addition, median plasma levels of IL8, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, PDGFR-B and TIMP1 proteins were significantly different between the non-malignant group and the gastric cancer group. The post-surgical levels of EpCAM, IGFBP3, IL8, CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1α, CCL20/MIP-3α, SPP1/OPN and PDGFR-B showed a uniform drop in all the samples studied.</p> <p>Conclusions</p> <p>Our study has identified several genes differentially expressed in gastric cancers, some for the first time. Some of these have been confirmed at the protein level, as well. Some of these proteins will need to be evaluated further for their potential as diagnostic biomarkers in gastric cancers and some could be useful as follow-up markers in gastric cancer.</p

Phase Diagram Of A Hard-sphere System In A Quenched Random Potential: A Numerical Study

We report numerical results for the phase diagram in the density-disorder plane of a hard sphere system in the presence of quenched, random, pinning disorder. Local minima of a discretized version of the Ramakrishnan-Yussouff free energy functional are located numerically and their relative stability is studied as a function of the density and the strength of disorder. Regions in the phase diagram corresponding to liquid, glassy and nearly crystalline states are mapped out, and the nature of the transitions is determined. The liquid to glass transition changes from first to second order as the strength of the disorder is increased. For weak disorder, the system undergoes a first order crystallization transition as the density is increased. Beyond a critical value of the disorder strength, this transition is replaced by a continuous glass transition. Our numerical results are compared with those of analytical work on the same system. Implications of our results for the field-temperature phase diagram of type-II superconductors are discussed.Comment: 14 pages, 10 postscript figures (included), submitted to Phys. Rev.

Possible robust insulator-superconductor transition on solid inert gas and other substrates

We present observations of the insulator-superconductor transition in ultrathin films of Bi on amorphous quartz, quartz coated with Ge, and for the first time, solid xenon condensed on quartz. The relative permeability $\epsilon_r$ ranges from 1.5 for Xe to 15 for Ge. Though we find screening effects as expected, the I-S transition is robust, and unmodified by the substrate. The resistance separatrix is found to be close to h/4e^2 and the crossover thickness close to $\rm 25 \AA$ for all substrates. I-V studies and Aslamazov-Larkin analyses indicate superconductivity is inhomogeneous. The transition can be understood in terms of a percolation model.Comment: accepted in Physical Review

The Magnetoelectric Effect in Transition Metal Oxides: Insights and the Rational Design of New Materials from First Principles

The search for materials displaying a large magnetoelectric effect has occupied researchers for many decades. The rewards could include not only advanced electronics technologies, but also fundamental insights concerning the dielectric and magnetic properties of condensed matter. In this article, we focus on the magnetoelectric effect in transition metal oxides and review the manner in which first-principles calculations have helped guide the search for (and increasingly, predicted) new materials and shed light on the microscopic mechanisms responsible for magnetoelectric phenomena.Comment: 24 pages, 12 figure

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors

Aim : To study the role of neoadjuvant imatinib mesylate in downsizing tumors in patients with locally advanced nonmetastatic gastrointestinal stromal tumors (GISTs), thus improving the possibility of complete resection. Materials and Methods : We used neoadjuvant imatinib in six patients with locally advanced GISTs, at a dose of 400 mg daily, given orally in all patients for a median period of 3.5 months (range 1-20 months). All patients had a computerized tomography scan (CT scan) once before starting the treatment and a repeat CT scan 1 month after starting imatinib. Some patients had another CT scan done at 3 months. The tumor volume was calculated using the formula V=4/3 \u3c0r 3 . Results : Following imatinib therapy, the median reduction in the tumor volume was 40% (range 20-50%). Four of the six patients underwent successful complete resection of the tumor following neoadjuvant imatinib for a median period of 2 months, and are disease free after a median follow-up of 10.5 months (range 3-20 months). Two patients in whom the tumors were deemed to be operable after downsizing refused surgery and are continuing imatinib. Imatinib did not produce serious toxicity in any patient. Conclusion : Neoadjuvant imatinib can be used successfully in patients with locally advanced nonmetastatic GISTs to improve the rates of complete resection and reduce the chance of tumor spill. The optimal duration of neoadjuvant treatment needs to be tailored based on response assessment at frequent intervals to identify the ideal window period for surgery

Structure of L-tyrosyl-L-valine monohydrate, C<SUB>14</SUB>H<SUB>20</SUB>N<SUB>2</SUB>O<SUB>4</SUB>.H<SUB>2</SUB>o

Mr=298.34, orthorhombic, P212121, a=5.629(1), b=8.702(2), c=31.007(8)Å, V=1519(1)Å3, Z=4, Dm=1.31, Dx= 1.30Mgm-3,Cu Kα, λ=1.5418Å, μ=0.737mm-, F(000)= 640.0, T= 293K, final R= 0.071 for 1144 unique observed reflections. The crystal structure is stabilized by extensive hydrogen -bonding involving N and O atoms

Structure of a thionucleoside: 5'-deoxy-5',6-epithio-5,6-dihydro-2',3'-O-isopropylidene-3-methyluridine

C<SUB>13</SUB>H<SUB>18</SUB>N<SUB>2</SUB>OS, M<SUB>r</SUB>=314.35 orthorhombic,P2<SUB>1</SUB>2<SUB>1</SUB>2<SUB>1</SUB>, with a=39.526(4), b=6.607(2),c=5.661(2)Å,Z=4, V=1478.36Å<SUP>3</SUP>, D<SUB>c</SUB>=1.412 Mgm<SUP>-3</SUP>, Cu Kα radiation. Final R = 0·073 for 1154 observed counter reflections. The sulphur atom is in a pseudo-equatorial position with respect to the dihydrouracil ring. The sugar pucker is predominantly O(l')exo unlike the C(3')-exo,C(4'}endo observed for 2'.3'·O·isopropylideneuridine (lSPU). The five­ membered dioxolane ring has C(7) displaced by 0·497 (7) Å from the best plane through atom, 0(2'), C(2'), e(3'), 0(3'), in contrast to ISPU where 0(3') shows the maximum deviation