Σάββατο 5 Αυγούστου 2017

Vitamin D Receptor Gene Polymorphism: Association with Susceptibility to Early-Onset Breast Cancer in Iranian, BRCA1/2 -Mutation Carrier and non-carrier Patients

Abstract

Mounting evidences support that vitamin D insufficiency or deficiency is a risk factor of breast cancer. Vitamin D receptor (VDR) is expressed in more than 36 cell types in different organs as in cancerous cells. Numerous allelic variants of VDR gene have been identified in human populations. Association of FokI (rs2228570) and BsmI (rs1544410) single nucleotide polymorphisms (SNPs) in VDR gene with the risk of breast cancer have been investigated in several studies, however, the published data are still inconsistent. Here, we investigated BsmI and FokI polymorphisms in Iranian young (≤ 35 years old) breast cancer patient with known BRCA1/2 germline mutations. VDR gene polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis in a cohort of 203 breast cancer patients and 214 controls from Iran. There was a significant association between the bb and Bb genotypes of the BsmI and the increased risk of breast cancer (OR 1.74, CI 1.06–2.87 and OR 2.08, CI 1.31–3.29, respectively). This association was maintained in the subgroup of BRCA1/2 mutation non carriers (OR 1.90, CI 1.15–3.20 and OR 1.75, CI 1.07–2.87 for bb and Bb genotypes respectively) and in the subgroup of BRCA1/2 mutation non-carriers with a family history of breast and/or ovarian cancer (OR 1.81, CI 1.08–3.05 and OR 1.65, CI 1.00–2.70 for bb and Bb genotypes respectively). None of the FokI homozygous or heterozygous genotypes were associated with the risk of breast cancer. In summary, the BsmI polymorphism of VDR gene may be associated with the risk of breast cancer in Iranian women.



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Preclinical validation of 111In-girentuximab-F(ab′)2 as a tracer to image hypoxia related marker CAIX expression in head and neck cancer xenografts

Hypoxia is a major cause of radio- and chemoresistance. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker and an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment. The radioactive tracer 111In-girentuximab-F(ab′)2 targets CAIX and can be used for SPECT imaging. Aim of this study was to validate and optimize 111In-girentuximab-F(ab′)2 for imaging of CAIX expression in head and neck tumor xenografts.

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Vitamin D Receptor Gene Polymorphism: Association with Susceptibility to Early-Onset Breast Cancer in Iranian, BRCA1/2 -Mutation Carrier and non-carrier Patients

Abstract

Mounting evidences support that vitamin D insufficiency or deficiency is a risk factor of breast cancer. Vitamin D receptor (VDR) is expressed in more than 36 cell types in different organs as in cancerous cells. Numerous allelic variants of VDR gene have been identified in human populations. Association of FokI (rs2228570) and BsmI (rs1544410) single nucleotide polymorphisms (SNPs) in VDR gene with the risk of breast cancer have been investigated in several studies, however, the published data are still inconsistent. Here, we investigated BsmI and FokI polymorphisms in Iranian young (≤ 35 years old) breast cancer patient with known BRCA1/2 germline mutations. VDR gene polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis in a cohort of 203 breast cancer patients and 214 controls from Iran. There was a significant association between the bb and Bb genotypes of the BsmI and the increased risk of breast cancer (OR 1.74, CI 1.06–2.87 and OR 2.08, CI 1.31–3.29, respectively). This association was maintained in the subgroup of BRCA1/2 mutation non carriers (OR 1.90, CI 1.15–3.20 and OR 1.75, CI 1.07–2.87 for bb and Bb genotypes respectively) and in the subgroup of BRCA1/2 mutation non-carriers with a family history of breast and/or ovarian cancer (OR 1.81, CI 1.08–3.05 and OR 1.65, CI 1.00–2.70 for bb and Bb genotypes respectively). None of the FokI homozygous or heterozygous genotypes were associated with the risk of breast cancer. In summary, the BsmI polymorphism of VDR gene may be associated with the risk of breast cancer in Iranian women.



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Copyright-Page

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Contributors

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Contents

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Forthcoming Issues

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3





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Transplantation

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Aman Mahajan, Christopher Wray




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Overview of Immunosuppressive Therapy in Solid Organ Transplantation

Publication date: September 2017
Source:Anesthesiology Clinics, Volume 35, Issue 3
Author(s): Curtis D. Holt

Teaser

Mechanisms of rejection, new pharmacologic approaches, and genomic medicine are major foci for current research in transplantation. It is hoped that these new agents and personalized immunosuppression will provide for less toxic regimens that are effective in preventing both acute and chronic allograft rejection. Until new agents are available, practitioners must use various combinations of currently approved agents to find the best regimens for improved long-term outcomes.


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Selenium Deficiency Augments the Levels of Inflammatory Factors and Heat Shock Proteins via the Redox Regulatory Pathway in the Skeletal Muscles of Mice

Abstract

Dietary selenium (Se) deficiency is known to cause myodynia syndrome and Se influences immune responses by changing the expression of inflammatory cytokines and heat shock proteins (Hsps), but the details are not completely elucidated. In the present study, 72 1-day-old mice were divided into two groups; the first group was fed a Se-sufficient diet, while the second group was fed a Se-deficient diet. Skeletal muscles and blood samples were taken from all mice after 42 days of treatment. The activities of glutathione peroxidase (GPX) and glutathione (GSH), mRNA and protein expression levels of inflammatory cytokines (including TNF-α, inducible NO synthase, cyclooxygenase-2, and prostaglandin E synthases), protein expression levels of NF-κB, and the mRNA expression levels of Hsps in the skeletal muscles of mice were examined. The results showed that GPX and GSH activities were decreased, while the mRNA and protein expression levels of inflammatory cytokines and the mRNA levels of Hsps were increased by Se deficiency in mouse skeletal muscles. In the present study, the protective role of Se in oxidative stress, inflammatory cytokines, and Hsps in the skeletal muscles of mice was summarized.



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Robotic device-assisted knee extension training during the early postoperative period after opening wedge high tibial osteotomy: a case report

Maintenance or restoration of a good range of motion of the knee is one of the most important outcomes following knee surgery. According to previous studies, opening wedge high tibial osteotomy enables better ...

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Somatostatin Analogs: How we choose, and why

Publication date: Available online 4 August 2017
Source:Seminars in Oncology
Author(s): Diane Reidy-Lagunes, Nitya Raj, Leonard Saltz




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In reply

Publication date: Available online 4 August 2017
Source:Seminars in Oncology
Author(s): Michele Boisdron-Celle, Olivier Capitain, Roger Faroux, Christophe Borg, Jean Philippe Metges, Marie Pierre Galais, Mehdi Kaassis, Jaafar Bennouna, Karine Bouhier-Leporrier, Eric Francois, Isabelle Baumgaertner, Véronique Guerin-Meyer, Oana Cojocarasu, Celia Roemer-Becuwe, Claire Stampfli, Ludovic Rosenfeld, Thierry Lecompte, Virginie Berger, Alain Morel, Erick Gamelin




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Comparison of the RECIST and EORTC PET criteria in the tumor response assessment: a pooled analysis and review

Abstract

Purpose

The EORTC PET criteria (EORTC criteria) are used to assess metabolic tumor response in patients with solid tumors. We conducted this pooled study to compare tumor responses according to the RECIST and EORTC criteria.

Methods

Electronic databases were searched for eligible articles with the terms of "RECIST" or "EORTC criteria". We found seven articles with the data on the comparison of tumor responses by the RECIST and EORTC criteria.

Results

A total of 181 patients were recruited from the seven studies. Ninety-two patients (50.8%) received cytotoxic chemotherapy and 89 were treated with targeted agents. The agreement of tumor responses between the RECIST and EORTC criteria was moderate (k = 0.493). Of 181 patients, 66 (36.5%) showed disagreement in the tumor responses: tumor response was upgraded in 54 patients and downgraded in 12 when adopting the EORTC criteria. The estimated overall response rates were significantly different between the two criteria (52.5% by the EORTC vs. 29.8% by the RECIST, P < 0.0001). When comparing the two criteria according to the anti-cancer treatments (chemotherapy or targeted therapy), the levels of agreement in tumor responses were not excellent (k = 0.461 for chemotherapy and k = 0.524 for targeted therapy, respectively) regardless of therapeutic types.

Conclusion

This pooled study indicates that the concordance of tumor responses between the RECIST and EORTC criteria is not excellent. When adopting the EORTC criteria instead of the RECIST, the overall response rate was significantly increased.



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Trisomy 12 assessment by conventional fluorescence in-situ hybridization (FISH), FISH in suspension (FISH-is) and laser scanning cytometry (LSC) in chronic lymphocytic leukemia.

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Publication date: Available online 4 August 2017
Source:Cancer Genetics
Author(s): Cuc H. Do, Karen M. Lower, Cindy Macardle, Bryone J. Kuss
Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, and prognostication is based on common genetic abnormalities which are detected by standard cytogenetic methods. However, current methods are restricted by the low number of cells able to be analyzed, resulting in the potential to miss clinically relevant sub-clonal populations of cells. A novel high throughput methodology called fluorescence in situ hybridization in suspension (FISH-IS) incorporates a flow cytometry-based imaging approach with automated analysis of thousands of cells. Here we have demonstrated that the FISH-IS technique is applicable to aneuploidy detection in CLL samples for a range of chromosomes using appropriate centromere probes. This method is able to accurately differentiate between monosomy, disomy and trisomy with a sensitivity of 1% in CLL. An analysis comparing conventional FISH, FISH-IS and laser scanning cytometry (LSC) is presented.



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Stereotactic Radiosurgery with or without Whole Brain Radiotherapy for Limited Brain Metastases: A Secondary Analysis of the NCCTG N0574 (Alliance) Randomized Controlled Trial

Publication date: Available online 5 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas M. Churilla, Karla V. Ballman, Paul D. Brown, Erin L. Twohy, Kurt Jaeckle, Elana Farace, Jane H. Cerhan, S. Keith Anderson, Xiomara W. Carrero, Yolanda I. Garces, Fred G. Barker, Richard Deming, Jesse G. Dixon, Stuart H. Burri, Caroline Chung, Cynthia Ménard, Volker W. Stieber, Bruce E. Pollock, Evanthia Galanis, Jan C. Buckner, Anthony L. Asher
BackgroundThere are conflicting data regarding a potential survival benefit to adjuvant whole brain radiotherapy (WBRT) among patients with limited brain metastases treated with stereotactic radiosurgery (SRS). We sought to determine if WBRT is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis.MethodsIn the N0574 trial, patients with 1-3 brain metastases were randomized to receive SRS or SRS+WBRT with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using two separate cut-points (> 2.0 vs. <2.0 and > 2.5 vs. < 2.5).ResultsA total of 126 NSCLC patients were included for analysis with median follow up of 14.2 months. Data for DS-GPA calculation was available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score > 2.0 and 23.0% of patients had DS-GPA scores > 2.5. The SRS and SRS+WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA > 2.0 (favorable prognoses, p=0.63; HR, 0.86; 95%CI, 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA < 2.0 patients (unfavorable prognoses, p=0.85; HR, 0.95; 95%CI, 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA > 2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (p=0.53).ConclusionsWe observed no significant differences in survival according to receipt of WBRT in favorable prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases.

Teaser

There are conflicting data regarding whether adjuvant whole brain radiotherapy (WBRT) improves survival among patients with 1-3 brain metastases and favorable prognostic factors. Our post-hoc analysis of the N0574 trial demonstrated that overall survival did not differ according to the use of WBRT among non-small cell lung cancer patients with favorable (p=0.63) or unfavorable (p=0.85) diagnosis-specific graded prognostic assessment scores. In patients with limited (1-3) brain metastases, stereotactic radiosurgery alone remains a preferred treatment approach.


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The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report

Abstract

Background

The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases.

Case presentation

We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches.

Conclusions

This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure.



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Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up

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Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Shannon K. Barth, Erin K. Dursa, Robert M. Bossarte, Aaron I. Schneiderman
ObjectivePrevious mortality studies of U.S. Gulf War veterans through 2000 and 2004 have shown an increased risk of brain cancer mortality among some deployed individuals. When veterans possibly exposed to environmental contaminants associated with demolition of the Khamisiyah Ammunition Storage Facility at Khamisiyah, Iraq, have been compared to contemporaneously deployed unexposed veterans, the results have suggested increased risk for mortality from brain cancer among the exposed. Brain cancer mortality risk in this cohort has not been updated since 2004.MethodsThis study analyzes the risk for brain cancer mortality between 1991–2011 through two series of comparisons: U.S. Gulf War deployed and non-deployed veterans from the same era; and veterans possibly exposed to environmental contaminants at Khamisiyah compared to contemporaneously deployed but unexposed U.S. Gulf War veterans. Risk of brain cancer mortality was determined using logistic regression. Life test hazard models were created to plot comparisons of annual hazard rates. Joinpoint regression models were applied to assess trends in hazard rates for brain cancer mortality.ResultsU.S. Army veterans possibly exposed at Khamisiyah had similar rates of brain cancer mortality compared to those not possibly exposed; however, veterans possibly exposed had a higher risk of brain cancer in the time period immediately following the Gulf War.ConclusionResults from these analyses suggest that veterans possibly exposed at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups.



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High-risk family colorectal cancer screening service in Ireland: Critical review of clinical outcomes

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Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Margaret Walshe, Robert Moran, Marie Boyle, Ion Cretu, Zita Galvin, Victoria Swan, Jason Trikovic, Michael P. Farrell, Sinéad Foy, Loretta O'Brien, Jan Leyden, Niall Mulligan, Helen Fenlon, David J. Gallagher, Padraic MacMathúna
BackgroundWe present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes.MethodsQuestionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy. We report neoplastic yield, examining effect of risk category, age, gender, and index colonoscopy findings.ResultsBetween 1998 and 2013, 2242 individuals were referred; 57.3% female, 42.7% male, median age 46 years (range9-85yrs). Median follow up time was 7.9yrs (range 0.5-15.3yrs). Follow up data after exclusion (non-compliance, known CRC) was available in 1496 (66.7%): 'Moderate risk' 785 (52.5%), HNPCC 256 (17.1%), (suspected) genetic syndrome (non-HNPCC) 85 (5.7%), 'Low Risk' 370 (24.7%). Screening was performed in 1025(68.5%) patients; colonoscopy data available for 993 (96.9%); total 1914 colonoscopies. At index colonoscopy, 178 (18.0%) patients had adenomas; 56 (5.5%) advanced adenoma. During the entire study period, 240 (24.2%) had an adenoma; 69 (7.0%) advanced adenoma. Cancers were diagnosed on screening in 2 patients. Older age and male gender were associated with higher adenoma detection rate; p<0.001, p=0.01, respectively. Risk category did not affect adenoma yield. Adenoma and advanced adenoma detection at index colonoscopy were associated with detection of same at follow up screening; p<0.001.ConclusionMale gender and age (>50) were the core identifiable risk factors for neoplasia at screening colonoscopy in this family screening setting. Our results would support less intensive surveillance in younger patients (<50), particularly where index colonoscopy is normal.



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SHP2 overexpression enhances the invasion and metastasis of ovarian cancer in vitro and in vivo

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A practical guide to the handling and administration of talimogene laherparepvec in Europe

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Trends in cervical cancer incidence and mortality in Poland: is there an impact of the introduction of the organised screening?

Abstract

Aside from existing opportunistic screening, an organised screening programme (OSP) for cervical cancer (CC) was implemented in 2006/2007 in Poland. We applied joinpoint regression and age-period-cohort model to look for the impact of the OSP on CC incidence/mortality trends. Decline of age-standardised incidence rates (ASIRs) in the screening-age group (25–59 years) accelerated from −2.2% (95% CI −2.7 to −1.7%) between 1993 and 2008 to −6.1% (95% CI −7.7 to −4.4%) annually after 2008. In women aged 60+ years, ASIRs declined from 1986 until 2005 [annual percent change (APC) = −2.6%, 95% CI −2.9 to −2.4%] and stabilised thereafter. Decline of age-standardised mortality rates (ASMRs) in the screening-age group accelerated from −1.3% (95% CI −1.5 to −1.1%) between 1980 and 2005 to −4.7% (95% CI −5.6 to −3.8%) annually after 2005. In women aged 60+ ASMR declined between 1991 and 2004 (APC = −2.9%, 95% CI −3.5 to −2.3%) and stabilised thereafter. Relative risks of CC diagnosis and death were 0.63 (95% CI 0.62–0.65) and 0.61 (95% CI 0.59–0.63), respectively, for the most recent period compared to the reference around 1982. Implementation of the OSP possibly accelerated downward trends in the burden of CC in Polish women under the age of 60, but recent stabilisation of trends in older women requires actions.



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Targeting Immune System Alterations in Hodgkin Lymphoma

Abstract

Purpose of Review

This review discusses novel immunotherapeutic approaches to treat Hodgkin lymphoma (HL), specifically PD-1 inhibitors and cellular immunotherapy.

Recent Findings

PD-1 inhibitors have shown promising results in the treatment of relapsed or refractory HL, leading to FDA approval of nivolumab and pembrolizumab, although complete remissions are rare. Chimeric antigen receptor T cells directed against CD30 have been investigated with preliminary clinical trials showing minimal toxicities and some responses in heavily pre-treated patients with HL.

Summary

HL is unique as it consists of a small percentage of malignant cells (Hodgkin Reed Sternberg cells) surrounded by an inflammatory microenvironment which promotes tumor growth and suppresses immune responses, making it an ideal target for immunotherapeutic approaches, such as PD-1 inhibitors and cellular immunotherapy. Current research is focused on overcoming barriers to efficacy via rational combinations that overcome resistance to therapy.



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A review of oral cannabinoids and medical marijuana for the treatment of chemotherapy-induced nausea and vomiting: a focus on pharmacokinetic variability and pharmacodynamics

Abstract

Purpose

Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV.

Methods

A PubMed search of the English-language literature available through 4 January 2017 was conducted to identify relevant articles for inclusion in the review.

Results

Oral cannabinoids have been shown to have similar or improved efficacy compared with conventional antiemetics for the resolution of nausea and/or vomiting in patients with cancer. However, oral THC has high PK variability, with variability in oral dronabinol peak plasma concentrations (C max) estimated between 150 and 200%. A new oral dronabinol solution has decreased intraindividual variability (area under the curve) vs oral dronabinol capsules. Further, oral THC has a slower time to C max compared with THC administered intravenously (IV) or by smoking, and a lower systemic availability than IV or smoked THC. The PD profile (e.g., "high") of oral THC differs from that of IV or smoked THC in healthy individuals. Oral cannabinoids are associated with greater incidence of adverse effects compared with conventional antiemetic therapy or placebo (e.g., dizziness, hypotension, and dysphoria or depression).

Conclusions

A new formulation of oral cannabinoids (i.e., dronabinol oral solution) minimized the PK/PD variability currently observed with capsule formulations.



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High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases

Abstract

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P < 0.001), in both adenocarcinoma (60.5 vs. 30.6%, P = 0.003) and squamous carcinoma (37.5 vs. 0%, P = 0.04). The incidence of BMs in patients with EGFR mutations was higher than in patients with wild-type EGFR (70.3 vs. 38.1%, P = 002). NSCLC patients with BMs had a higher incidence of EGFR mutations and those with mutant EGFR had a higher frequency of BMs. EGFR mutations may promote brain metastasis growth of NSCLC.



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The European society of regional anesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us?.

Purpose of review: To summarize the two recent sets of European and American Societies of Regional Anesthesia (ESRA-ASRA) Practice Advisory Guidelines for the performance of pediatric regional anesthesia (PRA). Recent findings: Owing to the still ongoing debate regarding crucial issues concerning the effective and safe conduct of PRA and because of the lack of any generally accepted guidelines regarding PRA the (ESRA-ASRA) have addressed these in two topical publications. Summary: Following an extensive literature search and an evidence-based approach the ESRA-ASRA task force have now provided a practice advisory on the following hot topics in PRA: the safety and appropriateness of placing block during general anesthesia or deep sedation, the use of test dosing, whether to use air or saline when performing loss-of-resistance, the risk of masking an acute compartment syndrome by use of PRA, dosing of local anesthetics for neuroaxial nerve blocks as well as peripheral nerve blocks, and finally the use of various drugs as adjuncts to local anesthetics. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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A comparative study of Ki-67 antigen expression between luminal A and triple-negative subtypes of breast cancer

Abstract

Tumor biomarkers such as hormone receptors, HER-2 and Ki-67 are used routinely in clinical practice for classification of molecular subtypes of breast cancer. Cell proliferation evaluated by Ki-67 antigen expression is important to determine tumor aggressiveness. However, there is a paucity of studies comparing Ki-67 expression in an expressive number of cells among molecular subtypes of breast cancer, particularly among less and more aggressive tumors, such as luminal A and triple-negative, which have led us to the present study. The current study included invasive ductal carcinoma samples of 59 patients, which were divided into two groups: luminal A (n = 29) and triple-negative (n = 30). For immunohistochemical reaction, the samples were incubated with monoclonal anti-Ki-67 antibody (clone MIB1) and cells expressing Ki-67 protein were identified by dark brown staining of the nuclei, counting at least 600 cells per slide. The mean percentages of stained nuclei were analyzed by Student's t test (p < 0.05). The mean percentage of nuclei stained with anti-ki-67 was 10.14 and 77.22 in luminal A and triple-negative breast cancers, respectively (p < 0.0001). Our study showed a high cell proliferation of triple-negative breast cancer in comparison with luminal A, justifying its aggressiveness and poor clinical outcome.



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Lower Selenoprotein T Expression and Immune Response in the Immune Organs of Broilers with Exudative Diathesis Due to Selenium Deficiency

Abstract

The objective of the present study was to investigate whether dietary selenium (Se) deficiency would affect the expression of selenoprotein T (SelT) and immune response in the immune organs of broilers. Changes in expression of inflammatory cytokines and oxidative stress response caused by Se deficiency can lead to organism damage, which in turn leads to immune response. Sixty (1-day-old) broilers were divided into the control group and Se-deficiency group. Animal models with exudative diathesis were duplicated in the broilers by feeding them Se-deficient diet for 20 days. After the Se-deficient group exhibited symptoms of exudative diathesis, all the broilers were euthanized, and their immune organs were taken for analysis. The tissues including spleen, bursa of Fabricius, and thymus were treated to determine the pathological changes (including microscopic and ultramicroscopic), the messenger RNA (mRNA) expression levels of SelT and its synthetase (SecS and SPS1), cytokine mRNA expression levels, and antioxidant status. The microscopic and ultramicroscopic analyses showed that immune tissues were obviously injured in the Se-deficient group. The mRNA expression of SelT was decreased compared with that in the control group. Meanwhile, the mRNA expression levels of SecS and SPS1 were downregulated. In the Se-deficient group, the mRNA expression levels of IL-1R and IL-1β were higher than those of three control organs. Additionally, the IL-2 and INF-γ mRNA expression levels were lower than those of the control group. The activity of CAT was decreased, and the contents of H2O2 and •OH were increased due to Se deficiency. Pearson method analysis showed that the expression of SelT had a positive correlation with IL-2, INF-γ, SecS, and SPS1 and a negative correlation with IL-1R and IL-1β. In summary, these data indicated that Se-deficient diet decreased the SelT expression and its regulation of oxidative stress, and it inhibited a pleiotropic mechanism of the immune response.



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Preventive effect of a vapocoolant spray on propofol-induced pain: a prospective, double-blind, randomized study

Abstract

Purpose

Propofol causes injection pain. Although lidocaine pre-treatment via venous occlusion is known to be the most effective way, it still has some inconvenience. We implemented this study to compare the effect of a vapocoolant spray with lidocaine pre-treatment.

Methods

Participants (n = 90) were randomized to one of three groups. Group V: after placebo injection and tourniquet, the vapocoolant spray was applied; group L: after lidocaine injection and tourniquet, the placebo spray was applied; group C: after placebo injection and tourniquet, the placebo spray was applied. The intensity of propofol-induced pain, the incidence of metallic taste, and the satisfaction were assessed.

Results

Propofol-induced pain was significantly lower in groups V and L than in group C [0.5 (0–2.25), 0.5 (0–1), and 5 (1–7), median (interquartile range), respectively, p < 0.001]. There was no significant difference in pain intensity between groups V and L. Group L showed a significantly higher incidence of metallic taste than groups V and C (23, 0, and 0%, respectively; p = 0.001). Groups V and L showed higher satisfaction scores than group C [5 (4–5), 4 (3.75–5), and 2 (2–3), respectively; p < 0.001], and there was a significant difference between groups V and L (p = 0.012).

Conclusion

Vapocoolant spray showed a similar effect to lidocaine in analgesia and lowered the incidence of a metallic taste. These resulted in greater satisfaction with the vapocoolant spray compared with lidocaine. Vapocoolant spray is an effective and convenient way to prevent propofol-induced pain.



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Pre-eclampsia and acute pulmonary embolism—the importance of making a differential diagnosis: a case report

Abstract

We describe the case of a 41-year-old pregnant patient who presented at 38 weeks of gestation for an urgent cesarean section, with new onset of pre-eclampsia as the initial diagnosis. The intraoperative course was complicated by seizures and hemodynamic collapse. Initially, the presentation of seizure pointed to pre-eclampsia/eclampsia; however, with careful consideration of each event as it occurred, the correct diagnosis was later determined to be pulmonary embolism and stroke. This case illustrates the importance of considering multiple possible etiologies, even when a particular diagnosis seems obvious.



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