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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 30 Σεπτεμβρίου 2017
Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report
Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis pati...
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Identification of keratin 19-positive cancer stem cells associating human hepatocellular carcinoma using CYFRA 21-1
Abstract
The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19+ patients than in K19− patients (P < 0.01). Receiver operating characteristic analyses revealed that serum CYFRA 21-1 was the statistically significant and the most sensitive predictor of tumor K19 expression among preoperative laboratory test values (P < 0.001). In HCC cells encoding with a K19 promoter-driven enhanced green fluorescent protein, fluorescence-activated cell sorting (FACS)-isolated K19+ cells displayed significantly higher levels of supernatant CYFRA 21-1 than K19− cells (P < 0.01). Gain/loss of K19 function experiments confirmed that CYFRA 21-1 levels were regulated by K19 function in HCC cells. Furthermore, CYFRA 21-1 levels reflected the treatment efficacy of LY2157299 in K19+ cells. In conclusion, CYFRA 21-1 can be used to predict K19 expression in HCC, and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs.
Keratin 19 (K19) is known to be a cancer stem cells (CSCs) marker in hepatocellular carcinoma (HCC). However, easily-measurable surrogate marker of K19 + HCC-CSCs has not been identified. This study showed that serum CYFRA 21-1 is the significant predictor of K19 expression in human HCC, and that CYFRA 21-1 levels reflect K19 function and TGFβ receptor 1 inhibitor treatment efficacy in HCC cells.
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Identification of keratin 19-positive cancer stem cells associating human hepatocellular carcinoma using CYFRA 21-1
Abstract
The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19+ patients than in K19− patients (P < 0.01). Receiver operating characteristic analyses revealed that serum CYFRA 21-1 was the statistically significant and the most sensitive predictor of tumor K19 expression among preoperative laboratory test values (P < 0.001). In HCC cells encoding with a K19 promoter-driven enhanced green fluorescent protein, fluorescence-activated cell sorting (FACS)-isolated K19+ cells displayed significantly higher levels of supernatant CYFRA 21-1 than K19− cells (P < 0.01). Gain/loss of K19 function experiments confirmed that CYFRA 21-1 levels were regulated by K19 function in HCC cells. Furthermore, CYFRA 21-1 levels reflected the treatment efficacy of LY2157299 in K19+ cells. In conclusion, CYFRA 21-1 can be used to predict K19 expression in HCC, and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs.
Keratin 19 (K19) is known to be a cancer stem cells (CSCs) marker in hepatocellular carcinoma (HCC). However, easily-measurable surrogate marker of K19 + HCC-CSCs has not been identified. This study showed that serum CYFRA 21-1 is the significant predictor of K19 expression in human HCC, and that CYFRA 21-1 levels reflect K19 function and TGFβ receptor 1 inhibitor treatment efficacy in HCC cells.
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Bladder-sparing radiotherapy for muscle-invasive bladder cancer: A survey of providers to determine barriers and enablers
To understand barriers and enablers to use of curative-intent radiotherapy (RT) for muscle-invasive bladder cancer using the Theoretical Domains Framework (TDF).
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Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: A case–control study from India
Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Bhawna Gupta, Freddie Bray, Narinder Kumar, Newell W Johnson
ObjectiveThis study examines the association between the incidence of oral cancer in India and oral hygiene habits, diet, chewing and smoking tobacco, and drinking alcohol. We also assessed the effects of oral hygiene habits with oral cancer risk among chewers versus never chewers.MethodsA hospital-based case–control study was conducted in Pune, India, based on face-to-face interviews, anthropometry, and intra-oral examinations conducted for 187 oral cancer cases and 240 controls.ResultsPoor oral hygiene score was associated with a significant risk of oral cancer (adjusted OR=6.98; 95%CI 3.72–13.05). When stratified by tobacco-chewing habit, the poor oral hygiene score was a significant risk factor only among ever tobacco chewers (adjusted OR=14.74; 95%CI 6.49–33.46) compared with never chewers (adjusted OR=0.71; 95%CI 0.14–3.63). Dental check-ups only at the time of pain by ever-chewers with poor oral hygiene was associated with an elevated risk (adjusted OR=4.22; 95%CI 2.44–7.29), while consumption of green, yellow, and cruciferous vegetables and citrus fruits was protective. A linear dose–response association was observed between oral cancer and chewing tobacco in terms of age at initiation, duration, and frequency of chewing per day (P<0.001). Smoking more than 10 bidis/cigarettes per day (adjusted OR=2.74; 95%CI 1.28–5.89) and for a duration >25 years (adjusted OR=2.31; 95%CI 1.14–4.71) elevated the risk of oral cancer.ConclusionGood oral hygiene habits – as characterized by healthy gums, brushing more than once daily, use of toothpaste, annual dental check-ups, and a minimal number of missing teeth – can reduce the risk of oral cancer significantly. In addition to refraining from chewing/smoking tobacco, a diet adequate in fruits and vegetables may protect against the disease.
Graphical abstract
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Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: A case–control study from India
Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Bhawna Gupta, Freddie Bray, Narinder Kumar, Newell W Johnson
ObjectiveThis study examines the association between the incidence of oral cancer in India and oral hygiene habits, diet, chewing and smoking tobacco, and drinking alcohol. We also assessed the effects of oral hygiene habits with oral cancer risk among chewers versus never chewers.MethodsA hospital-based case–control study was conducted in Pune, India, based on face-to-face interviews, anthropometry, and intra-oral examinations conducted for 187 oral cancer cases and 240 controls.ResultsPoor oral hygiene score was associated with a significant risk of oral cancer (adjusted OR=6.98; 95%CI 3.72–13.05). When stratified by tobacco-chewing habit, the poor oral hygiene score was a significant risk factor only among ever tobacco chewers (adjusted OR=14.74; 95%CI 6.49–33.46) compared with never chewers (adjusted OR=0.71; 95%CI 0.14–3.63). Dental check-ups only at the time of pain by ever-chewers with poor oral hygiene was associated with an elevated risk (adjusted OR=4.22; 95%CI 2.44–7.29), while consumption of green, yellow, and cruciferous vegetables and citrus fruits was protective. A linear dose–response association was observed between oral cancer and chewing tobacco in terms of age at initiation, duration, and frequency of chewing per day (P<0.001). Smoking more than 10 bidis/cigarettes per day (adjusted OR=2.74; 95%CI 1.28–5.89) and for a duration >25 years (adjusted OR=2.31; 95%CI 1.14–4.71) elevated the risk of oral cancer.ConclusionGood oral hygiene habits – as characterized by healthy gums, brushing more than once daily, use of toothpaste, annual dental check-ups, and a minimal number of missing teeth – can reduce the risk of oral cancer significantly. In addition to refraining from chewing/smoking tobacco, a diet adequate in fruits and vegetables may protect against the disease.
Graphical abstract
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Clinicopathological study of a dimorphic variant of breast carcinoma
Abstract
Background
Dimorphic cells have abundant clear cytoplasm similar to myoepithelial cells, and the nuclei are identical to those in adjacent malignant columnar epithelial cells. A dimorphic variant of a breast carcinoma involves a neoplastic proliferation of epithelial cells including dimorphic cells.
Methods
The subjects were patients with primary breast carcinoma, who underwent surgical resection at the Hospital of Dokkyo Medical University between 2000 and 2016, and were reviewed and diagnosed with a dimorphic variant of breast carcinoma.
Results
Dimorphic ICs typically showed a low-grade tumor and Hormonal receptor (HR) (estrogen and/or progesterone)+/HER2− subtype. Age, mean tumor size, status of nodal metastasis, stage and disease-free survival and overall survival did not differ between dimorphic and non-dimorphic ICs. The dimorphic cells were negative for p63 and cytokeratin 5/6 and 14 in most cases. In contrast, dimorphic cells were positive for HR, androgen receptor, and showed marked membrane-associated staining for E-cadherin and cytoplasmic staining for gross cystic disease fluid protein 15.
Conclusions
The morphological features of dimorphic cells may be confused with cells of other origins if the features of the dimorphic cells are not recognized. However, the typical morphological architecture of this carcinoma and expression of immunohistochemical markers support the diagnosis.
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Cancers, Vol. 9, Pages 134: The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Cancers, Vol. 9, Pages 134: The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Cancers doi: 10.3390/cancers9100134
Authors: Monica Fedele Laura Cerchia Gennaro Chiappetta
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state through a process of dedifferentiation that confers stem-like features, including chemoresistance, as well as the capacity to migrate and invade. Understanding the complex events that lead to the acquisition of a mesenchymal phenotype will therefore help to design new therapies against metastatic breast cancer. Here, we recapitulate the main endogenous molecular signals involved in this process, and their cross-talk with paracrine factors. These signals and cross-talk include the extracellular matrix; the secretome of cancer-associated fibroblasts, macrophages, cancer stem cells, and cancer cells; and exosomes with their cargo of miRNAs. Finally, we highlight some of the more promising therapeutic perspectives based on counteracting the epithelial-to-mesenchymal transition in breast cancer cells.
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Cancers, Vol. 9, Pages 134: The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Cancers, Vol. 9, Pages 134: The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Cancers doi: 10.3390/cancers9100134
Authors: Monica Fedele Laura Cerchia Gennaro Chiappetta
Breast cancer is a heterogeneous disease that is characterized by a high grade of cell plasticity arising from the contribution of a diverse range of factors. When combined, these factors allow a cancer cell to transition from an epithelial to a mesenchymal state through a process of dedifferentiation that confers stem-like features, including chemoresistance, as well as the capacity to migrate and invade. Understanding the complex events that lead to the acquisition of a mesenchymal phenotype will therefore help to design new therapies against metastatic breast cancer. Here, we recapitulate the main endogenous molecular signals involved in this process, and their cross-talk with paracrine factors. These signals and cross-talk include the extracellular matrix; the secretome of cancer-associated fibroblasts, macrophages, cancer stem cells, and cancer cells; and exosomes with their cargo of miRNAs. Finally, we highlight some of the more promising therapeutic perspectives based on counteracting the epithelial-to-mesenchymal transition in breast cancer cells.
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Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer
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MicroRNA signature in the chemoprevention of functionally-enriched stem and progenitor pools (FESPP) by Active Hexose Correlated Compound (AHCC)
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Activation of estrogen receptor α by estradiol and cisplatin induces platinum-resistance in ovarian cancer cells
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Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?
Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with ...
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β-catenin-mediated YAP signaling promotes human glioma growth
Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas a...
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Impact of Video Technology for Improving Success of Medial Canthus Episcleral Anesthesia in Ophthalmology.
Background and Objectives: Efficient learning of regional anesthesia in ophthalmology remains challenging because trainees are afforded limited opportunity to practice ocular anesthesia. The aim of this prospective, randomized, blinded study was to determine whether teaching with video improves regional anesthesia skills of residents in ophthalmology. Methods: From January to October 2016, 32 novice anesthesiology residents were evaluated while performing medial canthus episcleral procedures during a 5-day rotation. Residents were randomly assigned to either receive or not receive a video review of their performance at day 3. The primary outcome was a comparison of akinesia using a 12-point scale before incision assessed by the blinded surgeon. Results: A total of 288 blocks were performed by 32 residents and were assessed by 3 surgeons before the intervention (144 blocks) and after the intervention (144 blocks). Residents in the review group improved to a greater degree compared with residents in the no-review group. The median overall akinesia scores for the review and no-review groups were similarly low (6; interquartile range [IQR], 2-11; and 6 [IQR, 2-9], respectively) on day 1 of the rotation, whereas anesthesia performed by residents in the video group provided a better akinesia score (12 [IQR, 10-12] vs 8 [IQR, 6-10]; P
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The Technology of Video Laryngoscopy.
Tracheal intubation via laryngeal exposure has evolved over the past 150 years and has greatly expanded in the last decade with the introduction and development of newer, more sophisticated optical airway devices. The introduction of indirect and video-assisted laryngoscopes has significantly impacted airway management as evidenced by the presence of these devices in the majority of published difficult airway algorithms. However, it is quite possible that many airway managers do not have a thorough comprehension of how these devices actually function, an understanding that is vital not only for their use but also for assessing the devices' limitations. This article discusses the development of video laryngoscopy, how the video laryngoscope works, and the impact of video laryngoscopy on difficult airway management. (C) 2017 International Anesthesia Research Society
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General Anesthesia Imposes Negative Effects on Heart Rate and Blood Pressure Regulation in Patients With a History of Head and Neck Radiation Therapy.
BACKGROUND: Head and neck radiation therapy (HNRT) impairs baroreflex sensitivity, and it may potentiate the effects of anesthetics on heart rate (HR) and blood pressure (BP) regulation. Currently, the impacts of HNRT on HR and BP under anesthesia remain unclear. METHODS: In this study, 472 patients with primary oral cavity or oropharyngeal cancer at all stages were examined. Half of the patients underwent HNRT plus surgery. The other half underwent surgery only and was matched with the treatment patients according to age, sex, and body mass index at a 1:1 ratio. The HRs and BPs in the 2 groups during anesthetic induction, skin incision, and emergence were compared retrospectively. A multivariable model of repeated measures with unstructured covariance structure was used to examine the associations of HNRT with intraoperative HRs and BPs after adjusting for baseline HR and BP, time, use of [beta]-blockers, history of chemotherapy, and American Society of Anesthesiologists physical status score. BPs and HRs were collected every 5 minutes. The baseline HR and BP measurements were not included in the outcome vector and were only used as adjustment for baselines. RESULTS: Compared with corresponding baseline values in controls, the baseline HR was significantly higher (P = .0012) and the baseline systolic BP was lower (P
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Maternal Death Due to Amniotic Fluid Embolism: A National Study in France.
BACKGROUND: A structured definition of amniotic fluid embolism (AFE) based on 4 criteria was recently proposed for use in research by the Society for Maternal-Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation. The main objective of this study was to review all AFE-related maternal deaths in France during 2007-2011 according to the presence or not of all these 4 diagnostic criteria. METHODS: Maternal deaths due to AFE were identified by the national experts committee of the French Confidential Enquiry into Maternal Deaths during 2007-2011 (n = 39). The maternal mortality ratio for AFE was calculated. We applied the structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation to AFE-related maternal deaths identified by the national experts committee. Characteristics of women, pregnancies and deliveries; clinical and biological features of AFE; and specific laboratory tests used were described by the presence or not of all 4 diagnostic criteria. Management of obstetric hemorrhage and quality of care according to the experts were also described. RESULTS: The maternal mortality ratio from AFE was 0.95/100,000 live births (95% confidence interval, 0.67-1.3). Detailed clinical data were collected for 36 women who died from AFE: 21 (58%) had all 4 proposed diagnostic criteria and 15 (42%) had 1 or more missing criterion. Documented early disseminated intravascular coagulopathy was missing for 14 women, and 2 women exhibited more than 1 missing criterion. Ten of the 15 women with missing criteria had clinical coagulopathy, with standard hemostasis tests performed in only 3. Specific diagnostic examinations for AFE were performed in similar proportions by the presence or not of all diagnostic criteria. Opportunities to improve care included timely performance of indicated hysterectomy (n = 13) and improved transfusion practices (n = 9). In the context of maternal cardiac arrest, for 5 of 13 women, fetal extraction was performed within 5 minutes. CONCLUSIONS: The structured definition of AFE for research studies would exclude more than one-third of AFE-related maternal deaths identified by the national experts committee. Inclusion of clinical coagulopathy as a diagnostic criterion for AFE would reduce this proportion to 14%. There is still room for improvement in the management of obstetric hemorrhage and timely fetal extraction in the context of maternal cardiac arrest, frequently observed in AFE-related maternal death. (C) 2017 International Anesthesia Research Society
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Monte Carlo Simulations Comparing Fisher Exact Test and Unequal Variances t Test for Analysis of Differences Between Groups in Brief Hospital Lengths of Stay.
BACKGROUND: We examined type I and II error rates for analysis of (1) mean hospital length of stay (LOS) versus (2) percentage of hospital LOS that are overnight. These 2 end points are suitable for when LOS is treated as a secondary economic end point. METHODS: We repeatedly resampled LOS for 5052 discharges of thoracoscopic wedge resections and lung lobectomy at 26 hospitals. RESULTS: Unequal variances t test (Welch method) and Fisher exact test both were conservative (ie, type I error rate less than nominal level). The Wilcoxon rank sum test was included as a comparator; the type I error rates did not differ from the nominal level of 0.05 or 0.01. Fisher exact test was more powerful than the unequal variances t test at detecting differences among hospitals; estimated odds ratio for obtaining P
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Research Productivity and Rankings of Anesthesiology Departments in Canada and the United States: The Relationship Between the h-Index and Other Common Metrics.
BACKGROUND: To evaluate the relative research productivity and ranking of anesthesiology departments in Canada and the United States, using the Hirsch index (h-index) and 4 other previously validated metrics. METHODS: We identified 150 anesthesiology departments in Canada and the United States with an accredited residency program. Publications for each of the 150 departments were identified using Thomson's Institute for Scientific Information Web of Science, and the citation report for each department was exported. The bibliometric data were used to calculate publication metrics for 3 time periods: cumulative (1945-2014), 10 years (2005-2014), and 5 years (2010-2014). The following group metrics were then used to determine the publication impact and relative ranking of all 150 departments: h-index, m-index, total number of publications, sum of citations, and average number of citations per article. Ranking for each metric were also stratified by using a proxy for departmental size. The most common journals in which US and Canadian anesthesiology departments publish their work were identified. RESULTS: The majority (23 of the top 25) of top-ranked anesthesiology departments are in the United States, and 2 of the top 25 departments (University of Toronto; McGill University) are in Canada. There was a strong positive relationship between each of h-index, total number of publications, and the sum of citations (0.91-0.97; P
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