Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): A patterns of failure analysis

INTRODUCTION: Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. METHODS: One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. RESULTS: Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053). CONCLUSIONS: Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC

CYP3A4 and CYP3A5 genotyping by Pyrosequencing

BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection

Interaction between PPARA genotype and β-blocker treatment influences clinical outcomes following acute coronary syndromes

β-blockers (BB) are strongly recommended after an acute coronary syndrome (ACS), although all patients may not benefit. Causes for variable patient responses to BB are unknown. Given that myocardial ischemia and BB influence metabolic processes regulated by peroxisome proliferator-activated receptor α (PPARα), we hypothesized that interactions between polymorphisms of the PPARα gene (PPARA) and BB treatment would influence clinical outcome following ACS

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

<p>Abstract</p> <p>Background</p> <p>Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies.</p> <p>Methods</p> <p>Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients.</p> <p>Results</p> <p>We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). <it>CYP3A4*1B</it>, <it>CYP3A5*3 </it>and <it>CYP3A5*6 </it>alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. <it>CYP3A5*1/CYP3A5*1 </it>and <it>CYP3A5*1/CYP3A5*3 </it>genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin.</p> <p>Conclusion</p> <p>A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.</p

Contribution of Cell Surface Hydrophobicity in the Resistance of Staphylococcus aureus against Antimicrobial Agents

Staphylococcus aureus is found in a wide variety of habitats, including human skin, where many strains are commensals that may be clinically significant or contaminants of food. To determine the physiological characteristics of resistant strain of Staphylococcus aureus against pediocin, a class IIa bacteriocin, a resistant strain was compared with wild type in order to investigate the contribution of hydrophobicity to this resistance. Additional clumping of resistant strain relative to wild type in light microscopy was considered as an elementary evidence of resistance attainment. A delay in log phase attainment was observed in resistant strain compared to the wild type strain. A significant increase in cell surface hydrophobicity was detected for resistant strain in both hexadecane and xylene indicating the contribution of cell surface hydrophobicity as adaptive reaction against antimicrobial agents

Supplementation of Labneh with Passion Fruit Peel Enhanced Survival of E. coli Nissle 1917 during Simulated Gastrointestinal Digestion and Adhesion to Caco-2 Cells

Passion fruit peel powder (PFPP) was used to supplement the probiotic labneh to increase the activity of Escherichia coli Nissle 1917 (EcN) during production and storage. Labneh was manufactured with PFPP (0.5% and 1%) and analyzed at 0, 7, and 15 days of cold storage for postacidification and sensory properties and viability of EcN, survival of EcN to simulated gastrointestinal tract stress, and adhesion potential of EcN to Caco-2 cells. Acidification kinetics during fermentation showed that supplementation with PFPP reduced the time needed to decrease pH and reach the maximum acidification rate. PFPP addition contributed to postacidification of labneh during storage. PFPP had a beneficial effect (p &lt; 0.05) on counts of EcN in labneh during different storage periods. Consumer preference expectations for labneh enriched with PFPP (0.5% and 1%) were higher than those for the control. PFPP provided a significant protective action for EcN during simulated gastrointestinal transit and had a positive effect on EcN adhesion to Caco-2 cells in vitro, although this decreased during storage with labneh. Labneh supplementation with PFPP can be recommended because of the positive effect on EcN viability and the high nutritional value, which may increase the appeal of the product to consumers

Comparison of accelerated partial breast irradiation via multicatheter interstitial brachytherapy versus whole breast radiation

<p>Abstract</p> <p>Background</p> <p>Brachytherapy as adjuvant treatment for early-stage breast cancer has become widely available and offers patients an expedited treatment schedule. Given this, many women are electing to undergo brachytherapy in lieu of standard fractionation radiotherapy. We compare outcomes between patients treated with accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy versus patients who were also eligible for and offered APBI but who chose whole breast radiation (WBI).</p> <p>Methods</p> <p>Patients treated from December 2002 through May 2007 were reviewed. Selection criteria included patients with pTis-T2N0 disease, ≤ 3 cm unifocal tumors, and negative margins who underwent breast conservation surgery. Local control (LC), cause-specific (CSS) and overall survival (OS) were analyzed.</p> <p>Results</p> <p>202 patients were identified in the APBI cohort and 94 patients in the WBI cohort. Median follow-up for both groups exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories did not predict worse outcomes.</p> <p>Conclusion</p> <p>APBI via multicatheter interstitial brachytherapy provides similar local failure rates compared to WBI at 5 years for properly selected patients. Excellent results were seen despite the high fraction of younger patients (< 60 years old) and patients with DCIS.</p