Cytokine-induced killer cells have been used as an adjuvant treatment for hepatocellular carcinoma with curative treatment. However, the outcomes remain controversial.
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The US Centers for Disease Control recommends hepatitis C virus (HCV) screening for baby boomers. Spain presents a similar distribution of infected patients. We performed a cross sectional prospective study to evaluate the prevalence of undiagnosed HCV infection in subjects born between 1949 and 1974.
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Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization.
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Over the last two decades, exercise of the core muscles has gained major interest in professional sports. Research has focused on injury prevention and increasing athletic performance. We analyzed the guidelines for so-called functional strength training for back pain prevention and found that programs were similar to those for back pain rehabilitation; even the arguments were identical. Surprisingly, most exercise specifications have neither been tested for their effectiveness nor compared with the load specifications normally used for strength training. Analysis of the scientific literature on core stability exercises shows that adaptations in the central nervous system (voluntary activation of trunk muscles) have been used to justify exercise guidelines. Adaptations of morphological structures, important for the stability of the trunk and therefore the athlete's health, have not been adequately addressed in experimental studies or in reviews. In this article, we explain why the guidelines created for back pain rehabilitation are insufficient for strength training in professional athletes. We critically analyze common concepts such as 'selective activation' and training on unstable surfaces.
Nonalcoholic fatty liver disease (NAFLD) may occur secondarily to several medical conditions. Celiac sprue is the prototypic intestinal condition leading to diverse liver changes, including steatosis/steatohepatitis via increased intestinal permeability [1,2]. Olmersartan has consistently been associated with sprue-like enteropathy [3,4]. Hence, it is tempting to speculate that, similar to what occurs in celiac sprue, liver injury could be a common finding also in olmesartan-induced enteropathy.
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Cytokine-induced killer cells have been used as an adjuvant treatment for hepatocellular carcinoma with curative treatment. However, the outcomes remain controversial.
from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2ahZuZi
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The US Centers for Disease Control recommends hepatitis C virus (HCV) screening for baby boomers. Spain presents a similar distribution of infected patients. We performed a cross sectional prospective study to evaluate the prevalence of undiagnosed HCV infection in subjects born between 1949 and 1974.
from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2aFhOiD
via IFTTT
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization.
from Gastroenterology via xlomafota13 on Inoreader http://ift.tt/2aSyNdN
via IFTTT
Over the last two decades, exercise of the core muscles has gained major interest in professional sports. Research has focused on injury prevention and increasing athletic performance. We analyzed the guidelines for so-called functional strength training for back pain prevention and found that programs were similar to those for back pain rehabilitation; even the arguments were identical. Surprisingly, most exercise specifications have neither been tested for their effectiveness nor compared with the load specifications normally used for strength training. Analysis of the scientific literature on core stability exercises shows that adaptations in the central nervous system (voluntary activation of trunk muscles) have been used to justify exercise guidelines. Adaptations of morphological structures, important for the stability of the trunk and therefore the athlete's health, have not been adequately addressed in experimental studies or in reviews. In this article, we explain why the guidelines created for back pain rehabilitation are insufficient for strength training in professional athletes. We critically analyze common concepts such as 'selective activation' and training on unstable surfaces.
Nonalcoholic fatty liver disease (NAFLD) may occur secondarily to several medical conditions. Celiac sprue is the prototypic intestinal condition leading to diverse liver changes, including steatosis/steatohepatitis via increased intestinal permeability [1,2]. Olmersartan has consistently been associated with sprue-like enteropathy [3,4]. Hence, it is tempting to speculate that, similar to what occurs in celiac sprue, liver injury could be a common finding also in olmesartan-induced enteropathy.
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Genetic redirection of T lymphocytes allows us to unleash these potent cellular immune effectors against cancer. Chimeric antigen receptor (CAR) T cells are the best-in-class example that genetic engineering of T cells can lead to deep and durable responses, as has been shown in several clinical trials for CD19+ B cell malignancies. As a consequence, in the last few years, several academic institutions and commercial partners have started developing anti-CD19 CAR T cell products. Although most of these T cell products are highly effective in vivo, basic differences among them can generate different performance characteristics and thereby impact their long-term clinical outcome. Several strategies are being implemented in order to solve the current open issues of CART19 therapy: (i) increasing efficacy against indolent B cell leukemias and lymphomas, (ii) avoiding or preventing antigen-loss relapses, (iii) reducing and managing toxicity, and (iv) bringing this CART therapy to routine clinical practice. The field of CART therapies is thriving, and exciting new avenues are opening for both scientists and patients.
Metastatic renal cell carcinoma (mRCC) continues to be associated with high rates of morbidity and mortality. Renal cell carcinoma (RCC) is typically resistant to cytotoxic chemotherapy, and while targeted therapies have activity and prolong progression-free and overall survival, responses are usually not durable. Modulating the immune system with cytokine therapy, vaccine therapy, cell therapy, and checkpoint inhibitors offers hope of prolonged survival. Standard and emerging immune therapy approaches and combinations of immune therapies and other modalities are reviewed.
To identify potential risk factors for the development of jaw osteoradionecrosis (ORN) after 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) among patients with newly diagnosed h...
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Correlation of cognitive and masticatory function in Alzheimer's disease:
Association of FOXE1 polyalanine repeat region with thyroid cancer is dependent on tumour size:
Genetic susceptibility to cutaneous melanoma in southern Switzerland: role of CDKN2A, MC1R and MITF:
Results Using Korean Standard Series: A 5-year Retrospective Review.:
J Dermatolog Treat. 2016 Jul 28;:1-23
Authors: Yu DS, Kim HJ, Park YG, Bae JM, Kim JW, Lee YB
Abstract
BACKGROUND: There have been few studies regarding the results of the Korean standard patch test.
OBJECTIVES: The purpose of this study was to analyze the type and frequency of common contact allergens in Korea and to compare the results with those of previous reports.
METHODS: From June 2009 to June 2014, 330 patients with suspected allergic contact dermatitis who visited our clinic were tested using the Korean standard patch test.
RESULTS: The highest sensitization rate was found for nickel sulfate (47.58%). There was a significant gender difference in the prevalence of sensitization to nickel sulfate (OR = 2.41, P = 0.0004) and wool alcohol (OR = 2.85, P = 0.0358). Higher sensitization to nickel sulfate (OR = 1.18, P = 0.0159), 4-phenylenediamine (OR = 1.23, P= 0.003), and tixocortol-21-pivalte (OR 1.48, P = 0.0212) and lower sensitization to thimerosal (OR = 0.77, P = 0.0023) were associated with increasing age. Patients with allergic contact dermatitis on the scalp had a significantly higher risk of sensitization to 4-phenylenediamine (OR = 3.07, P = 0.0013). Patients with allergic contact dermatitis on the hands had significantly higher risks of sensitization to wool alcohol (OR = 3.44, P = 0.0083), formaldehyde (OR = 2.52, P = 0.0178), and colophony (OR = 2.05, P = 0.0499).
CONCLUSIONS: These results demonstrate trends in patch test results in Korea and the basis for the presumption of the route of allergen exposure.
PMID: 27469077 [PubMed - as supplied by publisher]
Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker.
Oncotarget. 2016 Jul 27;
Authors: Yu W, Ma Y, Shankar S, Srivastava RK
Abstract
SATB2 (special AT-rich binding protein-2), a transcription factor and chromatin modulator, regulates the expression of genes required for maintaining pluripotency and self-renewal. The molecular mechanisms by which human pancreatic normal ductal epithelial cells are transformed to cancer cells are not well understood. The main goal of the paper is to examine the molecular mechanisms by which SATB2 regulates transformation of human pancreatic normal ductal epithelial (HPNE) cells, and assess whether transformed HPNE cells gained the phenotypes of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in pancreatic CSCs, primary tissues and cell lines, but not in HPNE cells. SATB2 induces cellular transformation, stemness and epithelial to mesenchymal transition in HPNE cells, and inhibition of its expression suppresses these activities. Overexpression of SATB2 in HPNE cells resulted in induction of stem cell markers (CD44, CD24 and CD133), and transcription factors (Oct4, Sox2 and Nanog). SATB2 can directly bind to promoters of Bcl-2, Bsp, Nanog, c-Myc, XIAP, Klf4 and Hoxa2, suggesting the role of SATB2 in pluripotency, cell survival and proliferation. SATB2-overexpressing HPNE cells (HPNE/SATB2) formed tumors in Balb C nude mice, whereas HPNE/Empty vector cells did not form any tumor. Since SATB2 is highly expressed in human pancreatic cancer tissues and cell lines, but not in HPNE cells and normal pancreatic tissue, it can drive pancreatic cancer growth and metastasis. Our findings suggest that SATB2 can induce dedifferentiation by inducing stemness and may have a role in pancreatic carcinogenesis, and can be used as a diagnostic biomarker.
PMID: 27472393 [PubMed - as supplied by publisher]
Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues.
Oncotarget. 2016 Jul 27;
Authors: Chen W, Zhou J, Wu K, Huang J, Ding Y, Yun EJ, Wang B, Ding C, Hernandez E, Santoyo J, Chen H, Lin H, Sagalowsky A, He D, Zhou J, Hsieh JT
Abstract
Conventional chemotherapy is commonly used for advanced stages of transitional cell carcinoma (TCC) with modest success and high morbidity; however, TCC eventually develops resistance. Muscle invasive bladder cancer (MIBC) is recognized as a lethal disease due to its poor response to traditional chemotherapy. Numerous studies have implicated β-catenin, a critical effector in Wnt-mediated pathway associated with epithelial-mesenchymal transition and cancer stem cell, is involved in TCC progression, and furthermore closely associated with chemo-resistance. In this study, we discovered a novel natural product analogue CYD 6-17 that has a potent inhibitory effect on TCC cells exhibiting drug resistance to various chemotherapeutics, with an IC50 at nM range. Delivery of CYD 6-17 significantly inhibited the tumor growth using xenograft model but without detectable side effects. Mechanistically, it targeted β-catenin gene transcription by decreasing the binding of XBP1 to the promoter region, which appeared to be a new regulatory mechanism for β-catenin gene expression. Clinically, XBP1 expression correlated with the poor overall survival of patients. Overall, this study unveils unique mechanism of β-catenin gene regulation in advanced TCC and also offers a potential rational therapeutic regimen to MIBC.
PMID: 27472396 [PubMed - as supplied by publisher]
TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells.
Oncotarget. 2016 Jul 26;
Authors: Wang Y, Wang Y, Li GR
Abstract
The earlier study showed that lysophosphatidylcholine (lysoPC) induced apoptosis in human coronary artery smooth muscle cells (SMCs); however, the related molecular mechanisms are not fully understood. The present study investigated how lysoPC induces apoptosis in cultured human coronary artery SMCs using cell viability assay, flow cytometry, confocal microscopy, and molecular biological approaches. We found that lysoPC reduced cell viability in human coronary artery SMCs by eliciting a remarkable Ca2+ influx. The effect was antagonized by La3+, SKF-96365, or Pyr3 as well as by silencing TRPC1 or TRPC3. Co-immunoprecipitation revealed that TRPC1 and TRPC3 had protein-protein interaction. Silencing TRPC1 or TRPC3 countered the lysoPC-induced increase of Ca2+ influx and apoptosis, and the pro-apoptotic proteins Bax and cleaved caspase-3 and decrease of the anti-apoptotic protein Bcl-2 and the survival kinase pAkt. These results demonstrate the novel information that TRPC1/TRPC3 channels mediate lysoPC-induced Ca2+ influx and apoptosis via activating the pro-apoptotic proteins Bax and cleaved caspase-3 and inhibiting the anti-apoptotic protein Bcl-2 and the survival kinase pAkt in human coronary artery SMCs, which implies that TRPC1/TRC3 channels may be the therapeutic target of lysoPC-induced disorders such as atherosclerosis.
PMID: 27472391 [PubMed - as supplied by publisher]
IGF-1R inhibition sensitizes breast cancer cells to ATM-Related Kinase (ATR) inhibitor and cisplatin.
Oncotarget. 2016 Jul 27;
Authors: O'Flanagan CH, O'Shea S, Lyons A, Fogarty FM, McCabe N, Kennedy RD, O'Connor R
Abstract
The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-related kinase (ATR). We also observed a clear induction of DDR in cells that were exposed to IGF-1R TKIs (BMS-754807 and OSI-906) as indicated by accumulation of γ-H2AX, and phosphorylated Chk1. Combination of the IGF-1R/IR TKIs with an ATR kinase inhibitor VE-821 resulted in additive to synergistic cytotoxicity compared to either drug alone. In MCF-7 cells with stably acquired resistance to the IGF-1R TKI (MCF-7-R), DNA damage was also observed, and again, dual inhibition of the ATR kinase and IGF-1R/IR kinase resulted in synergistic cytotoxicity. Interestingly, dual inhibition of ATR and IGF-1R was more effective in MCF-7-R cells than parental cells. IGF-1R TKIs also potentiated the effects of cisplatin in a panel of breast cancer cell lines. Overall, our findings identify induction of DDR by IGF-1R kinase inhibition as a rationale for co-targeting the IGF-1R with ATR kinase inhibitors or cisplatin, particularly in cells with acquired resistance to TKIs.
PMID: 27472395 [PubMed - as supplied by publisher]
Dimerization of EGFR and HER2 induces breast cancer cell motility through STAT1-dependent ACTA2 induction.
Oncotarget. 2016 Jul 26;
Authors: Jeon M, You D, Bae SY, Kim SW, Nam SJ, Kim HH, Kim S, Lee JE
Abstract
The dimerization of EGFR and HER2 is associated with poor prognosis such as induction of tumor growth and cell invasion compared to when EGFR remains as a homodimer. However, the mechanism for events after dimerization in breast cancer models is not clear. We found that expressions of alpha-smooth muscle actin (ACTA2) and signal transducer and activator of transcription 1 (STAT1) significantly increased with transient or stable overexpression of HER2 in EGFR-positive breast cancer cells. ACTA2 and STAT1 expression was also increased in HER2-positive breast cancer patients. In contrast, ACTA2 expression was decreased by HER2 siRNA. Next, we investigated the co-relation between STAT1 and ACTA2 expression. Basal ACTA2 expression was significantly decreased by treatment with the STAT1 inhibitor fludarabine or the JAK2 inhibitor AG490. In contrast, ACTA2 expression was increased by STAT1 overexpression. Levels of ACTA2, STAT1, and HER2 were increased and relapse free survival was decreased in high-risk breast cancer patients. We also investigated the effect of ACTA2 on cell motility, which was suppressed by ACTA2 shRNA overexpression in MDA-MB231 HER2 and 4T1 mammary carcinoma cells. The number of lung metastatic nodules was significantly decreased in ACTA2 knockdown mice. Taken together, these results demonstrated that induction of ACTA2 by EGFR and HER2 dimerization was regulated through a JAK2/STAT1 signaling pathway, and aberrant ACTA2 expression accelerated the invasiveness and metastasis of breast cancer cells.
PMID: 27472389 [PubMed - as supplied by publisher]
'Open access' and the International Journal of Audiology.
Int J Audiol. 2016 Jul 29;:1-2
Authors:
PMID: 27472297 [PubMed - as supplied by publisher]
HER2 Immunohistochemistry-Guided Targeted Fluorescence In Situ Hybridization Analysis Does Not Help Identify Intratumoral Heterogeneity in Breast Cancer.
Arch Pathol Lab Med. 2016 Aug;140(8):741
Authors: Gulbahce HE, Factor R, Geiersbach K, Downs-Kelly E
PMID: 27472230 [PubMed - as supplied by publisher]
In Reply.
Arch Pathol Lab Med. 2016 Aug;140(8):741
Authors: Hammond ME, Hicks DG
PMID: 27472229 [PubMed - as supplied by publisher]
First-Line Immune Therapy-Implications for Pathologists.
Arch Pathol Lab Med. 2016 Aug;140(8):739-740
Authors: Miller RA, Cagle PT, Bernicker EH
PMID: 27472228 [PubMed - as supplied by publisher]
hTERT gene polymorphism correlates with the risk and the prognosis of thyroid cancer.
Cancer Biomark. 2016 Jul 8;
Authors: Gong L, Xu Y, Hu YQ, Ding QJ, Yi CH, Huang W, Zhou M
Abstract
OBJECTIVES: The study explored the association between rs10069690C/T and rs2736100G/T of human telomerase reverse transcriptase (hTERT) gene, and the prognosis of thyroid cancer.
METHODS: The study had 452 thyroid cancer patients recruited as case group who hospitalized in Jingzhou Central Hospital from January 2001 to June 2004 and 452 healthy people recruited as control group at the same area. The hTERT gene polymorphisms at rs10069690 C/T and rs2736100 G/T were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between patients' life quality and hTERT gene polymorphisms six months after surgery was evaluated based on the Cancer patients' quality of life index rating scale.
RESULTS: There were statistical differences in genotype and allele frequencies of rs10069690 C/T between the case group and control group (both P < 0.05). An association between rs10069690C/T polymorphism and an increased risk of thyroid cancer was shown by logistic regression analysis (CT vs. CC, OR = 1.333, 95%CI = 1.006-1.766, P = 0.045; TT vs. CC, OR = 1.910, 95%CI = 1.084-3.367, P = 0.023; CT + TT vs. CC, OR = 2.246, 95%CI = 1.078-1.840, P = 0.006; T vs. C, OR = 1.376, 95%CI = 1.104-1.715, P = 0.004). Genotype frequency of rs2736100G/T between the two groups had no statistical differences (P > 0.05). After stratification according to age, T stage, tumor size and tumor node metastasis (TNM) stage, the distribution frequencies of CC genotype and CT + TT genotype of rs10069690C/T showed significant difference (P < 0.05). The life quality of patients with CC genotype was better than that of patients with CT $+$ TT genotype. The results of Cox regression model multifactor analysis showed that age, T stage, tumor size and rs10069690C/T were independent risk factors of thyroid cancer prognosis.
CONCLUSIONS: hTERT gene polymorphism at rs10069690C/T is associated with the risk and prognosis of thyroid cancer, but hTERT gene polymorphism at rs2736100G/T is not.
PMID: 27472887 [PubMed - as supplied by publisher]
Organ Doses From Diagnostic Medical Radiography-Trends Over Eight Decades (1930 to 2010).
Health Phys. 2016 Sep;111(3):235-255
Authors: Melo DR, Miller DL, Chang L, Moroz B, Linet MS, Simon SL
Abstract
This study provides a retrospective assessment of doses to 13 organs for the most common radiographic examinations conducted between the 1930s and 2010, taking into account typical technical parameters used for radiography during those years. This study is intended to be a resource on changes in medical diagnostic radiation exposure over time with a specific purpose of supporting retrospective epidemiological studies of radiation health risks. The authors derived organ doses to the brain, esophagus, thyroid, red bone marrow, lungs, breast, heart, stomach, liver, colon, urinary bladder, ovaries, and testes based on 14 common radiographic procedures and compared, when possible, with doses reported in the literature. These dose estimates were based on radiographic exposure parameters described in textbooks widely used by radiologic technologists in training from 1939 to 2010. The derived estimated doses presented here are believed to be representative of typical organs for an average-size adult who might be considered to be similar to the reference person. There were large variations in organ doses noted among the different types of radiographic examinations. Doses were highest in organs within the area imaged and next highest in organs in close proximity to the area imaged. Estimated organ doses have declined substantially [overall 22-fold (±38)] over time as a consequence of changes in technology, imaging protocols and protective measures. For some examinations, only slight differences were observed in doses for the decades of the 1960s, 1970s, and 1980s due to minor changes in technical parameters. Substantial dose reductions were observed in the 1990s and 2000s.
PMID: 27472750 [PubMed - as supplied by publisher]
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| Related Articles |
Development of a simple genotyping method for the HLA-A*31:01-tagging SNP in Japanese.
Pharmacogenomics. 2015;16(15):1689-99
Authors: Maekawa K, Nakamura R, Kaniwa N, Mizusawa S, Kitamoto A, Kitamoto T, Ukaji M, Matsuzawa Y, Sugiyama E, Uchida Y, Kurose K, Ueta M, Sotozono C, Ikeda H, Yagami A, Matsukura S, Kinoshita S, Muramatsu M, Ikezawa Z, Sekine A, Furuya H, Takahashi Y, Matsunaga K, Aihara M, Saito Y, Japan Pharmacogenomics Data Science Consortium
Abstract
AIM: To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
MATERIALS & METHODS: DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay.
RESULTS: HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays.
CONCLUSION: Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.
PMID: 26490229 [PubMed - indexed for MEDLINE]
A neural network-based method for spectral distortion correction in photon counting x-ray CT.
Phys Med Biol. 2016 Jul 29;61(16):6132-6153
Authors: Touch M, Clark DP, Barber W, Badea CT
Abstract
Spectral CT using a photon counting x-ray detector (PCXD) shows great potential for measuring material composition based on energy dependent x-ray attenuation. Spectral CT is especially suited for imaging with K-edge contrast agents to address the otherwise limited contrast in soft tissues. We have developed a micro-CT system based on a PCXD. This system enables both 4 energy bins acquisition, as well as full-spectrum mode in which the energy thresholds of the PCXD are swept to sample the full energy spectrum for each detector element and projection angle. Measurements provided by the PCXD, however, are distorted due to undesirable physical effects in the detector and can be very noisy due to photon starvation in narrow energy bins. To address spectral distortions, we propose and demonstrate a novel artificial neural network (ANN)-based spectral distortion correction mechanism, which learns to undo the distortion in spectral CT, resulting in improved material decomposition accuracy. To address noise, post-reconstruction denoising based on bilateral filtration, which jointly enforces intensity gradient sparsity between spectral samples, is used to further improve the robustness of ANN training and material decomposition accuracy. Our ANN-based distortion correction method is calibrated using 3D-printed phantoms and a model of our spectral CT system. To enable realistic simulations and validation of our method, we first modeled the spectral distortions using experimental data acquired from (109)Cd and (133)Ba radioactive sources measured with our PCXD. Next, we trained an ANN to learn the relationship between the distorted spectral CT projections and the ideal, distortion-free projections in a calibration step. This required knowledge of the ground truth, distortion-free spectral CT projections, which were obtained by simulating a spectral CT scan of the digital version of a 3D-printed phantom. Once the training was completed, the trained ANN was used to perform distortion correction on any subsequent scans of the same system with the same parameters. We used joint bilateral filtration to perform noise reduction by jointly enforcing intensity gradient sparsity between the reconstructed images for each energy bin. Following reconstruction and denoising, the CT data was spectrally decomposed using the photoelectric effect, Compton scattering, and a K-edge material (i.e. iodine). The ANN-based distortion correction approach was tested using both simulations and experimental data acquired in phantoms and a mouse with our PCXD-based micro-CT system for 4 bins and full-spectrum acquisition modes. The iodine detectability and decomposition accuracy were assessed using the contrast-to-noise ratio and relative error in iodine concentration estimation metrics in images with and without distortion correction. In simulation, the material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with 50% and 20% reductions in material concentration measurement error in full-spectrum and 4 energy bins cases, respectively. Overall, experimental data confirms that full-spectrum mode provides superior results to 4-energy mode when the distortion corrections are applied. The material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with as much as a 41% reduction in material concentration measurement error for full-spectrum mode, while also bringing the iodine detectability to 4-6 mg ml(-1). Distortion correction also improved the 4 bins mode data, but to a lesser extent. The results demonstrate the experimental feasibility and potential advantages of ANN-based distortion correction and joint bilateral filtration-based denoising for accurate K-edge imaging with a PCXD. Given the computational efficiency with which the ANN can be applied to projection data, the proposed scheme can be readily integrated into existing CT reconstruction pipelines.
PMID: 27469292 [PubMed - as supplied by publisher]
 | Related Articles |
Retrospective dosimetry of Iodine-131 exposures using Iodine-129 and Caesium-137 inventories in soils--A critical evaluation of the consequences of the Chernobyl accident in parts of Northern Ukraine.
J Environ Radioact. 2015 Dec;150:20-35
Authors: Michel R, Daraoui A, Gorny M, Jakob D, Sachse R, Romantschuk LD, Alfimov V, Synal HA
Abstract
The radiation exposure of thyroid glands due to (131)I as a consequence of the Chernobyl accident was investigated retrospectively based on (129)I and (137)Cs inventories in soils in Northern Ukraine. To this end, soil samples from 60 settlements were investigated for (129)I, (127)I, and (137)Cs by AMS, ICP-MS and gamma-spectrometry, respectively. Sampling was performed between 2004 und 2007. In those parts of Northern Ukraine investigated here the (129)I and (137)Cs inventories are well correlated, the variability of the individual (129)I/(137)Cs ratios being, however, high. Both the (129)I and (137)Cs inventories in the individual 5 samples for each settlement allowed estimating the uncertainties of the inventories due to the variability of the radionuclide deposition and consequently of the retrospective dosimetry. Thyroid equivalent doses were calculated from the (129)I and the (137)Cs inventories using aggregated dose coefficients for 5-year old and 10-year-old children as well as for adults. The highest thyroid equivalent doses (calculated from (129)I inventories) were calculated for Wladimirowka with 30 Gy for 5-years-old children and 7 Gy for adults. In 35 settlements of contamination zone II the geometric mean of the thyroid equivalent doses was 2.0 Gy for 5-years-old children with a geometric standard deviation (GSD) of 3.0. For adults the geometric mean was 0.47 Gy also with a GSD of 3.0. In more than 25 settlements of contamination zone III the geometric means were 0.82 Gy for 5-years old children with a GSD of 1.8 and 0.21 Gy for adults (GSD 1.8). For 45 settlements, the results of the retrospective dosimetry could be compared with thyroid equivalent doses calculated using time-integrated (131)I activities of thyroids which were measured in 1986. Thus, a critical evaluation of the results was possible which demonstrated the general feasibility of the method, but also the associated uncertainties and limitations.
PMID: 26254721 [PubMed - indexed for MEDLINE]
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Sorption and desorption studies of radioiodine onto silver chloride via batch equilibration with its aqueous media.
J Environ Radioact. 2015 Dec;150:9-19
Authors: Mostafa M, Ramadan HE, El-Amir MA
Abstract
The uncontrolled spread out of radioiodine (especially (1)(3)(1)I) produced from nuclear activities or accidents, due to its high volatility, to the biosphere represents an environmental impact because of its concentration in the thyroid gland and accumulation on soil surface. This work represents a simple method for isolation of radioiodine from aqueous solution in the form of insoluble solid compound and further recovery of it in aqueous phase for any further controlled use. Crystalline silver chloride was prepared and characterized. Batch sorption of (131)I onto the prepared AgCl was studied from different aqueous media (H2O and NaOH of different concentrations) and at different I(-):Ag molar ratios (from alkaline media) for different times at 25 °C. It was found that the sorption yield of (131)I from 2.5 M NaOH solution (at I(-):Ag and S2O3(2-):I(-) molar ratios of 0.025 and 2, respectively) reached 97.7% after 6 h and only slightly increased to 98.6% after 16 h of contact time. The presence of H2O2 adversely affected the batch sorption process. The included REDOX and precipitation reactions were discussed. Batch desorption of the sorbed (131)I from AgCl into aqueous phase was studied with NaOCl solutions of different concentrations and different contact times at 25 °C. Desorption yield of (131)I was found to be 94.5% with 10 mL of 0.5 M NaOCl solution after contact time of 16 h. Kinetic analysis has been performed for both batch sorption and desorption processes.
PMID: 26254720 [PubMed - indexed for MEDLINE]
Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016 Jun 10;38(3):346-50
Authors:
Abstract
<strong>Objective </strong>To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). <strong>Methods </strong>Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. <strong>Results </strong> There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). <strong>Conclusion </strong>For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.
PMID: 27469924 [PubMed - in process]
A neural network-based method for spectral distortion correction in photon counting x-ray CT.
Phys Med Biol. 2016 Jul 29;61(16):6132-6153
Authors: Touch M, Clark DP, Barber W, Badea CT
Abstract
Spectral CT using a photon counting x-ray detector (PCXD) shows great potential for measuring material composition based on energy dependent x-ray attenuation. Spectral CT is especially suited for imaging with K-edge contrast agents to address the otherwise limited contrast in soft tissues. We have developed a micro-CT system based on a PCXD. This system enables both 4 energy bins acquisition, as well as full-spectrum mode in which the energy thresholds of the PCXD are swept to sample the full energy spectrum for each detector element and projection angle. Measurements provided by the PCXD, however, are distorted due to undesirable physical effects in the detector and can be very noisy due to photon starvation in narrow energy bins. To address spectral distortions, we propose and demonstrate a novel artificial neural network (ANN)-based spectral distortion correction mechanism, which learns to undo the distortion in spectral CT, resulting in improved material decomposition accuracy. To address noise, post-reconstruction denoising based on bilateral filtration, which jointly enforces intensity gradient sparsity between spectral samples, is used to further improve the robustness of ANN training and material decomposition accuracy. Our ANN-based distortion correction method is calibrated using 3D-printed phantoms and a model of our spectral CT system. To enable realistic simulations and validation of our method, we first modeled the spectral distortions using experimental data acquired from (109)Cd and (133)Ba radioactive sources measured with our PCXD. Next, we trained an ANN to learn the relationship between the distorted spectral CT projections and the ideal, distortion-free projections in a calibration step. This required knowledge of the ground truth, distortion-free spectral CT projections, which were obtained by simulating a spectral CT scan of the digital version of a 3D-printed phantom. Once the training was completed, the trained ANN was used to perform distortion correction on any subsequent scans of the same system with the same parameters. We used joint bilateral filtration to perform noise reduction by jointly enforcing intensity gradient sparsity between the reconstructed images for each energy bin. Following reconstruction and denoising, the CT data was spectrally decomposed using the photoelectric effect, Compton scattering, and a K-edge material (i.e. iodine). The ANN-based distortion correction approach was tested using both simulations and experimental data acquired in phantoms and a mouse with our PCXD-based micro-CT system for 4 bins and full-spectrum acquisition modes. The iodine detectability and decomposition accuracy were assessed using the contrast-to-noise ratio and relative error in iodine concentration estimation metrics in images with and without distortion correction. In simulation, the material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with 50% and 20% reductions in material concentration measurement error in full-spectrum and 4 energy bins cases, respectively. Overall, experimental data confirms that full-spectrum mode provides superior results to 4-energy mode when the distortion corrections are applied. The material decomposition accuracy in the reconstructed data was vastly improved following distortion correction and denoising, with as much as a 41% reduction in material concentration measurement error for full-spectrum mode, while also bringing the iodine detectability to 4-6 mg ml(-1). Distortion correction also improved the 4 bins mode data, but to a lesser extent. The results demonstrate the experimental feasibility and potential advantages of ANN-based distortion correction and joint bilateral filtration-based denoising for accurate K-edge imaging with a PCXD. Given the computational efficiency with which the ANN can be applied to projection data, the proposed scheme can be readily integrated into existing CT reconstruction pipelines.
PMID: 27469292 [PubMed - as supplied by publisher]
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Retrospective dosimetry of Iodine-131 exposures using Iodine-129 and Caesium-137 inventories in soils--A critical evaluation of the consequences of the Chernobyl accident in parts of Northern Ukraine.
J Environ Radioact. 2015 Dec;150:20-35
Authors: Michel R, Daraoui A, Gorny M, Jakob D, Sachse R, Romantschuk LD, Alfimov V, Synal HA
Abstract
The radiation exposure of thyroid glands due to (131)I as a consequence of the Chernobyl accident was investigated retrospectively based on (129)I and (137)Cs inventories in soils in Northern Ukraine. To this end, soil samples from 60 settlements were investigated for (129)I, (127)I, and (137)Cs by AMS, ICP-MS and gamma-spectrometry, respectively. Sampling was performed between 2004 und 2007. In those parts of Northern Ukraine investigated here the (129)I and (137)Cs inventories are well correlated, the variability of the individual (129)I/(137)Cs ratios being, however, high. Both the (129)I and (137)Cs inventories in the individual 5 samples for each settlement allowed estimating the uncertainties of the inventories due to the variability of the radionuclide deposition and consequently of the retrospective dosimetry. Thyroid equivalent doses were calculated from the (129)I and the (137)Cs inventories using aggregated dose coefficients for 5-year old and 10-year-old children as well as for adults. The highest thyroid equivalent doses (calculated from (129)I inventories) were calculated for Wladimirowka with 30 Gy for 5-years-old children and 7 Gy for adults. In 35 settlements of contamination zone II the geometric mean of the thyroid equivalent doses was 2.0 Gy for 5-years-old children with a geometric standard deviation (GSD) of 3.0. For adults the geometric mean was 0.47 Gy also with a GSD of 3.0. In more than 25 settlements of contamination zone III the geometric means were 0.82 Gy for 5-years old children with a GSD of 1.8 and 0.21 Gy for adults (GSD 1.8). For 45 settlements, the results of the retrospective dosimetry could be compared with thyroid equivalent doses calculated using time-integrated (131)I activities of thyroids which were measured in 1986. Thus, a critical evaluation of the results was possible which demonstrated the general feasibility of the method, but also the associated uncertainties and limitations.
PMID: 26254721 [PubMed - indexed for MEDLINE]
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Sorption and desorption studies of radioiodine onto silver chloride via batch equilibration with its aqueous media.
J Environ Radioact. 2015 Dec;150:9-19
Authors: Mostafa M, Ramadan HE, El-Amir MA
Abstract
The uncontrolled spread out of radioiodine (especially (1)(3)(1)I) produced from nuclear activities or accidents, due to its high volatility, to the biosphere represents an environmental impact because of its concentration in the thyroid gland and accumulation on soil surface. This work represents a simple method for isolation of radioiodine from aqueous solution in the form of insoluble solid compound and further recovery of it in aqueous phase for any further controlled use. Crystalline silver chloride was prepared and characterized. Batch sorption of (131)I onto the prepared AgCl was studied from different aqueous media (H2O and NaOH of different concentrations) and at different I(-):Ag molar ratios (from alkaline media) for different times at 25 °C. It was found that the sorption yield of (131)I from 2.5 M NaOH solution (at I(-):Ag and S2O3(2-):I(-) molar ratios of 0.025 and 2, respectively) reached 97.7% after 6 h and only slightly increased to 98.6% after 16 h of contact time. The presence of H2O2 adversely affected the batch sorption process. The included REDOX and precipitation reactions were discussed. Batch desorption of the sorbed (131)I from AgCl into aqueous phase was studied with NaOCl solutions of different concentrations and different contact times at 25 °C. Desorption yield of (131)I was found to be 94.5% with 10 mL of 0.5 M NaOCl solution after contact time of 16 h. Kinetic analysis has been performed for both batch sorption and desorption processes.
PMID: 26254720 [PubMed - indexed for MEDLINE]
'Open access' and the International Journal of Audiology.
Int J Audiol. 2016 Jul 29;:1-2
Authors:
PMID: 27472297 [PubMed - as supplied by publisher]
The Effects of Mandibular Advancement Device on Pressure Pain Threshold of Masticatory Muscles: A Prospective Controlled Cohort Study.
J Oral Facial Pain Headache. 2016 Summer;30(3):234-240
Authors: Alessandri-Bonetti G, Bortolotti F, Bartolucci ML, Marini I, D'Antò V, Michelotti A
Abstract
AIMS: To determine if pressure pain thresholds (PPTs) of masticatory and neck muscles change after the application of a mandibular advancement device (MAD) in patients with obstructive sleep apnea (OSA).
METHODS: A prospective study was conducted in a sample of 27 OSA patients (24 males and 3 females; mean age ± standard deviation [SD]: 54.8 ± 11.8, mean apnea-hypopnea index ± SD: 23.5 ± 13.3) and 27 age- and sex-matched healthy controls. Exclusion criteria were signs and symptoms of temporomandibular disorders (TMD), metabolic diseases, and use of antidepressants, analgesics, or anti-inflammatory drugs. A calibrated examiner evaluated PPTs of seven head and neck muscles bilaterally by using a Fischer algometer. In the OSA group, PPTs were recorded immediately before the MAD application (T₀), after 15 days (T₁), and after 6 months (T₂) of therapy; in the control group, PPTs were recorded at the same time intervals. PPT differences at baseline and over time within each group and between OSA and control groups were analyzed by Friedman and Mann-Whitney tests.
RESULTS: There were no PPT differences between groups at baseline. In the OSA group, PPTs of temporalis and masseter muscles decreased significantly at T₁ compared with T₀ (P < .05), but no differences were found at T₂. No significant PPT differences were found in the neck muscles or over time in the control group.
CONCLUSION: MAD application induces a decrease of PPTs of masticatory muscles at the beginning of the therapy, but a physiologic adaptation occurs by 6 months.
PMID: 27472526 [PubMed - as supplied by publisher]
The role of human papillomavirus in head and neck cancer and the impact on radiotherapy outcome.
Acta Otolaryngol. 2016 Jul 29;:1-8
Authors: Zhu X, Wang Y, Zhu H, Lou W
Abstract
CONCLUSION: HPV + HNSCC patients have improved Overall Survival (OS), Disease Specific Survival (DSS), Disease Free Survival (DFS), and Progression Free Survival (PFS). The radiotherapy treatment can't improve the Survival of the HPV-negative HNSCC patients.
OBJECTIVE: To investigate the role of Human papillomavirus in head and neck cancer and the impact on radiotherapy outcome.
METHODS: A search in PubMed and Chinese CNKI (2000-2015) was performed. This meta-analysis was done using RevMan 5.1 software. Outcomes included OS, DSS, DFS, PFS, and Treatment responses rates (RR).
RESULTS: A total of 2620 patients in 10 studies were included. The Positive detective rates of HPV and P16 are 32.5% (425/1309) and 42.5% (526/1239). OS and PFS were improved in HPV + patients compared to HPV - patients (HR = 0.48; 95% CI = 0.37-0.62, p < 0.0001) and (HR = 0.49; 95% CI = 0.31-0.78, p < 0.0001). The survival benefit was similar in HPV-16 + patients (adjusted HR = 0.39; 95% CI = 0.21-0.60, p < 0.0001). The DFS of P16 + patients improved (HR = 0.70; 95% CI = 0.55-0.89, p < 0.0001). The treatment response of p16 + patients didn't significantly improve compared with p16- patients (HR = 1.44; 95% CI = 1.01-2.05, p = 0.05).
PMID: 27472193 [PubMed - as supplied by publisher]
High-Risk Factors in Symptomatic Patients Undergoing Carotid Artery Stenting With Distal Protection: Buffalo Risk Assessment Scale (BRASS).
Neurosurgery. 2016 Jul 27;
Authors: Lownie SP, Pelz DM, Sharma M, Pandey SK, Boulton MR, Lee DH
PMID: 27471974 [PubMed - as supplied by publisher]
An assessment of olfactory function in patients with laryngopharyngeal reflux disease.
Acta Otolaryngol. 2016 Jul 29;:1-7
Authors: Emre Dinc M, Dalgic A, Avincsal MO, Ulusoy S, Celik A, Develioglu ON
Abstract
CONCLUSIONS: The results reported here indicate that there was a statistically significant difference in the olfactory functions of laryngopharyngeal reflux patients vs the healthy group. To the best of the authors' knowledge, this study is the first to evaluate the olfactory function of patients diagnosed with laryngopharyngeal reflux using an objective method, 24-h pH monitoring.
OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate olfactory functions in laryngopharyngeal reflux (LPR) patients and compare the results with healthy controls.
METHODS: A total of 60 participants; 30 men and women with a diagnosis of laryngopharyngeal reflux and 30 healthy controls, were included in the study. Patients in the laryngopharyngeal reflux group were evaluated by the Reflux Symptom Index (RSI), Reflux Finding Scores (RFS), and finally 24-h pH monitoring to confirm the diagnosis of laryngopharyngeal reflux. The Sniffin' Sticks olfactory test results of the laryngopharyngeal reflux and control groups were compared, and the relationship between the study findings and the olfactory parameters were evaluated.
RESULTS: The odor threshold, odor discrimination, odor identification, and TDI scores of the laryngopharyngeal reflux group were significantly lower than those of the control group. Also there was a statistically significant negative correlation detected between the olfactory test and some symptom and finding scores.
PMID: 27472044 [PubMed - as supplied by publisher]
House dust mite sublingual tablet is effective and safe in patients with allergic rhinitis.
Allergy. 2016 Jul 29;
Authors: Okamoto Y, Fujieda S, Okano M, Yoshida Y, Kakudo S, Masuyama K
Abstract
BACKGROUND: House dust mite (HDM) is the major indoor allergen for allergic diseases such as allergic rhinitis (AR) and asthma. Although sublingual immunotherapy (SLIT) is a curative treatment for HDM-induced AR, data from large-scale studies are limited. We evaluated the efficacy and safety of HDM tablets in adolescent and adult patients (aged 12-64 years) with HDM-induced AR with or without intermittent asthma.
METHODS: In a double-blind trial in Japan, 968 subjects were randomized 1:1:1 to 300 index of reactivity (IR), 500 IR, or placebo groups. The primary endpoint was the Average Adjusted Symptom Score (AASS) in the last 8 weeks of the 52-week treatment. Secondary endpoints included individual nasal and ocular symptom scores, rescue medication use, and the Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) scores.
RESULTS: The AASS in the last 8 weeks of treatment significantly improved in both the 300 IR and the 500 IR groups compared to that in the placebo group (p < 0.001). In the 300 IR group, the onset of action occurred at week 8-10. All four nasal symptoms significantly improved in both active treatment groups; rescue medication use and JRQLQ outcome improved in the 300 IR group. Most adverse events (AEs) were mild, and 16 serious AEs (SAEs) were reported; however, none of them were drug-related.
CONCLUSIONS: One-year treatment with 300 IR and 500 IR HDM tablets was effective without major safety concerns. The recommended therapeutic dose for AR is 300 IR. This article is protected by copyright. All rights reserved.
PMID: 27471838 [PubMed - as supplied by publisher]
Review of perforator flaps in head and neck cancer surgery.
Curr Opin Otolaryngol Head Neck Surg. 2016 Jul 28;
Authors: Cho A, Hall FT
Abstract
PURPOSE OF REVIEW: Perforator flaps are increasingly being used to reconstruct head and neck defects. They offer several advantages over nonperforator-based flaps with lower donor site morbidity and a versatile range of reconstructive options. The anterolateral thigh flap is well established in the head and neck and is a good example of a reliable perforator free flap. With the increasing use of both free and regional perforator-based flaps, it is timely to review their anatomy, clinical applications, and role in head and neck reconstruction. We also discuss increasingly popular perforator flaps such as the submental flap for the head and neck.
RECENT FINDINGS: The anterolateral thigh flap is now commonly used to reconstruct a wide variety of head and neck defects. The submental flap fills a niche role for reconstruction of intraoral defects.
SUMMARY: Perforator flaps are now mainstream reconstructive options in the head and neck surgeon's armamentarium.
PMID: 27471790 [PubMed - as supplied by publisher]
Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy.
Oncoimmunology. 2016 Jun;5(6):e1169356
Authors: Ishibashi K, Kumai T, Ohkuri T, Kosaka A, Nagato T, Hirata Y, Ohara K, Oikawa K, Aoki N, Akiyama N, Sado M, Kitada M, Harabuchi Y, Celis E, Kobayashi H
Abstract
Tumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4(+) helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8(+) cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G26-40 was effective in eliciting tumor-reactive CD4(+) T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G26-40-specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.
PMID: 27471649 [PubMed]
CTLA4 blockade reduces immature myeloid cells in head and neck squamous cell carcinoma.
Oncoimmunology. 2016 Jun;5(6):e1151594
Authors: Yu GT, Bu LL, Zhao YY, Mao L, Deng WW, Wu TF, Zhang WF, Sun ZJ
Abstract
Immature myeloid cells such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages play a vital role in the tumor immune escape and tumor progression. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4), as a negative immune checkpoint, is highly expressed in numerous solid tumors. However, precise functions of CTLA4 in head and neck squamous cell carcinoma (HNSCC) have not yet been elucidated. In this study, we demonstrated that the ratio of CD8(+)/CTLA4 can be used as a potential index with a clinical prognostic value for HNSCC. Using immunocompetent transgenic mouse model with spontaneous HNSCC, we directly observed that targeting CTLA4 decreases MDSCs and M2 macrophages and promotes T cell activation in both tumor microenvironment and macro-environment. In all, our study provides direct evidence in vivo and proposes a rationale for CTLA4 inhibition as a future therapeutic strategy in patients with HNSCC.
PMID: 27471622 [PubMed]
An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs.
Oncoimmunology. 2016 Jun;5(6):e1123368
Authors: Hirayama M, Tomita Y, Yuno A, Tsukamoto H, Senju S, Imamura Y, Sayem MA, Irie A, Yoshitake Y, Fukuma D, Shinohara M, Hamada A, Jono H, Yuba E, Kono K, Yoshida K, Tsunoda T, Nakayama H, Nishimura Y
Abstract
Insulin-like growth factor II mRNA-binding protein 3 (IMP-3), an oncofetal antigen identified using genome-wide cDNA microarray analyses, is overexpressed in several malignancies. IMP-3-derived cytotoxic T lymphocyte (CTL) epitopes have been used for peptide-based immunotherapies against various cancers. In addition to CTLs, induction of tumor-associated antigen (TAA)-specific helper T (Th) cells is crucial for establishment of effective antitumor immunity. In this study, we aimed to identify IMP-3-derived long peptides (IMP-3-LPs) carrying CTL and promiscuous Th-cell epitopes for use in cancer immunotherapy. IMP-3-derived Th-cell epitopes that bind to multiple HLA-class II molecules were predicted by in silico analysis, and their immunogenicity was determined by utilizing human T cells. We identified two highly immunogenic IMP-3-LPs presented by multiple HLA-class II molecules. One of the IMP-3-LPs encompassed two CTL epitopes that have been used for peptide-vaccine immunotherapy in ongoing clinical trials. IMP-3-LPs-specific Th cells responded to autologous dendritic cells (DCs) loaded with the recombinant IMP-3 proteins, suggesting that these s (LPs) can be naturally processed and presented. The IMP-3-LPs and specific Th cells augmented the expansion of IMP-3-specific CTLs, which was further enhanced by programmed cell death-1 (PD-1) blockade. In addition, IMP-3-LP encapsulated in liposomes was efficiently cross-presented in vitro, and this LP successfully cross-primed CTLs in HLA-A2 transgenic mice (Tgm) in vivo. Furthermore, one of the IMP-3-LPs induced IMP-3-specific Th cells from peripheral blood mononuclear cells (PBMCs) of head-and-neck malignant tumor (HNMT) patients. These findings suggest the potential usefulness of IMP-3-LPs in propagating both Th cells and CTLs and may have implications for IMP-3-LPs-based cancer immunotherapy.
PMID: 27471607 [PubMed]
The Expression Levels of XLF and Mutant P53 Are Inversely Correlated in Head and Neck Cancer Cells.
J Cancer. 2016;7(11):1374-82
Authors: Feng S, Rabii R, Liang G, Song C, Chen W, Guo M, Wei X, Messadi D, Hu S
Abstract
XRCC4-like factor (XLF), also known as Cernunnos, is a protein encoded by the human NHEJ1 gene and an important repair factor for DNA double-strand breaks. In this study, we have found that XLF is over-expressed in HPV(+) versus HPV(-) head and neck squamous cell carcinoma (HNSCC) and significantly down-regulated in the HNSCC cell lines expressing high level of mutant p53 protein versus those cell lines harboring wild-type TP53 gene with low p53 protein expression. We have also demonstrated that Werner syndrome protein (WRN), a member of the NHEJ repair pathway, binds to both mutant p53 protein and NHEJ1 gene promoter, and siRNA knockdown of WRN leads to the inhibition of XLF expression in the HNSCC cells. Collectively, these findings suggest that WRN and p53 are involved in the regulation of XLF expression and the activity of WRN might be affected by mutant p53 protein in the HNSCC cells with aberrant TP53 gene mutations, due to the interaction of mutant p53 with WRN. As a result, the expression of XLF in these cancer cells is significantly suppressed. Our study also suggests that XLF is over-expressed in HPV(+) HNSCC with low expression of wild type p53, and might serve as a potential biomarker for HPV(+) HNSCC. Further studies are warranted to investigate the mechanisms underlying the interactive role of WRN and XLF in NHEJ repair pathway.
PMID: 27471552 [PubMed]
