Purpose of review: The prevalence of IgE-mediated food allergy and anaphylaxis has risen rapidly in developed countries, and countries with rapid industrialization may follow. Therapies include elimination diets, Oral ImmunoTherapy, and the administration of biologics, but high serum IgE levels may preclude their use. Consequently, decreasing IgE becomes a rational approach and could be obtained by immunoapheresis. The aim of this review is to evaluate the rationale and advantages of immunoapheresis. Recent findings: The majority of the available adsorbers remove aspecifically all classes of immunoglobulins. Recently, IgE-specific adsorbers have been approved. Data on immunoapheresis for the treatment of allergic diseases with pathologically elevated IgE levels are emerging. In atopic dermatitis, this therapy alone seems to be beneficial. IgE-selective apheresis appears to be sufficient to reduce the risk of anaphylaxis in multiple food allergy (MFA) and, when IgE titers are high, to open the way to treatment with Omalizumab. Summary: Prospective studies, with well designed protocols, are needed to assess the efficacy, tolerability, and cost-effectiveness of immunoapheresis in the field of food allergy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Τρίτη 28 Μαρτίου 2017
The effect of requesting a reason for non-adherence to a guideline in a long running automated...
Background: Automated reminders are employed frequently to improve guideline adherence, but limitations of automated reminders are becoming more apparent. We studied the reasons for non-adherence in the setting of automated reminders to test the hypothesis that a separate request for a reason in itself may further improve guideline adherence. Methods: In a previously implemented automated reminder system on prophylaxis for postoperative nausea and vomiting (PONV), we included additional automated reminders requesting a reason for non-adherence. We recorded these reasons in the pre-operative screening clinic, the OR and the PACU. We compared adherence to our PONV guideline in two study groups with a historical control group. Results: Guideline adherence on prescribing and administering PONV prophylaxis (dexamethasone and granisetron) all improved compared to the historical control group (89 vs. 82% (p< 0.0001), 96 vs 95% (not significant) and 90 vs 82% (p<0.0001)) while decreasing unwarranted prescription for PONV prophylaxis (10 vs. 13 %). In the pre-operative screening clinic, the main reason for not prescribing PONV prophylaxis was disagreement with the risk estimate by the decision support system. In the OR/PACU, the main reasons for not administering PONV prophylaxis were: ‘unintended non-adherence’ and ‘failure to document’. Conclusions: In this study requesting a reason for non-adherence is associated with improved guideline adherence. The effect seems to depend on the underlying reason for non-adherence. It also illustrates the importance of human factors principles in the design of decision support. Some reasons for non-adherence may not be influenced by automated reminders....
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Implementation of a single sign-on system between practice, research and learning systems
Background: Multiple specialized electronic medical systems are utilized in the health enterprise. Each of these systems has their own user management, authentication and authorization process, which makes it a complex web for navigation and use without a coherent process workflow. Users often have to remember multiple passwords, login/logout between systems that disrupt their clinical workflow. Challenges exist in managing permissions for various cadres of health care providers. Objectives: This case report describes our experience of implementing a single sign-on system, used between an electronic medical records system and a learning management system at a large academic institution with an informatics department responsible for student education and a medical school affiliated with a hospital system caring for patients and conducting research. Methods: At our institution, we use OpenMRS for research registry tracking of interventional radiology patients as well as to provide access to medical records to students studying health informatics. To provide authentication across different users of the system with different permissions, we developed a Central Authentication Service (CAS) module for OpenMRS, released under the Mozilla Public License and deployed it for single sign-on across the academic enterprise. The module has been in implementation since August 2015 to present, and we assessed usability of the registry and education system before and after implementation of the CAS module. 54 students and 3 researchers were interviewed. Results: The module authenticates users with appropriate privileges in the medical records system, providing secure access with minimal disruption to their workflow. No passwords requests were sent and users reported ease of use, with streamlined workflow. Conclusions: The project demonstrates that enterprise-wide single sign-on systems should be used in healthcare to reduce complexity like “password hell”, improve usability and user navigation. We plan to extend this to work with other systems used in the health care enterprise....
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Systematic review and meta-analysis of venous thromboembolism in otolaryngology–head and neck surgery
Abstract
Background
The purpose of this study was to present our systematic review and meta-analysis of the data on venous thromboembolism (VTE; deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) in otolaryngology–head and neck surgery (OHNS).
Methods
PubMed and Scopus databases were searched for studies reporting VTE in OHNS. Incidence of VTE and bleeding is reported and meta-analyzed overall and for chemoprophylaxis and squamous cell carcinoma (SCC)/free flap subgroups.
Results
A total of 23 studies were included with a total of 618,264 patients. Incidence of VTE was 0.4%. The incidence of bleeding complications was 0.9%. The addition of chemoprophylaxis did not result in a decreased VTE incidence (odds ratio [OR], 0.86), but produced an increased risk of bleeding (OR, 3.78). The overall OR for VTE in SCC/free flap cases was 6.28.
Conclusion
Chemoprophylaxis may not be necessary in the OHNS non-SCC or free flap patient population and must be balanced against an increased risk of bleeding. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
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Improving outcomes in veterans with oropharyngeal squamous cell carcinoma through implementation of a multidisciplinary clinic
Abstract
Background
Treatment of head and neck cancer is complex, and a multidisciplinary clinic may improve the coordination of care. The value of a head and neck multidisciplinary clinic has not yet been established in oropharyngeal squamous cell carcinoma (SCC).
Methods
A retrospective review was conducted of Veterans Affairs patients with oropharyngeal SCC undergoing concurrent chemoradiation before and after implementation of the head and neck multidisciplinary clinic.
Results
Fifty-two patients before and 54 patients after multidisciplinary clinic were included in this study. Age, tobacco use, and p16+ status were similar between groups. With multidisciplinary clinic, time to treatment decreased, and utilization of supportive services, including speech pathology, dentistry, and nutrition increased. The 5-year disease-specific survival rate increased from 63% to 81% (p = .043) after implementation of the multidisciplinary clinic. Multivariate analysis showed that disease stage (p = .016), p16 status (p = .006), and multidisciplinary clinic participation (p = .042) were predictors of disease-specific survival.
Conclusion
Implementation of a multidisciplinary clinic improved care coordination and disease-specific survival in patients with oropharyngeal SCC. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
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Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection
Abstract
Background
Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high-risk features. The optimal radiation dose is unknown.
Methods
One thousand six hundred twenty-five eligible patients with head and neck MCC were identified in the National Cancer Data Base (NCDB). Radiation dose was divided into 3 groups: 30 to <50 Gray (Gy), 50-55 Gy, and >55-70 Gy. Cox regression was used to compare overall survival (OS) between groups, accounting for age, sex, stage, surgery type, margin status, comorbidities, and use of chemotherapy.
Results
With a median follow-up of 33.5 months, 3-year OS was 48.9%, 70.3%, and 58.7% for 30 to <50 Gy, 50-55 Gy, and >55-70 Gy, respectively (P < .001). Compared to 50-55 Gy, doses between 30 to <50 Gy (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.17-1.99; P = .002) and >55-70 Gy (adjusted HR 1.21; 95% CI 1.0-1.46; P = .06) were associated with worse survival.
Conclusion
Adjuvant radiation doses within 50-55 Gy may be optimal for head and neck MCC.
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Endocavitary sonography of early oral cavity malignant tumors
Abstract
Background
Preoperative staging is crucial for oral cancer management. The purpose of this study was to assess the tumor thickness using ultrasound and to correlate the level of histological infiltration with the tumor superficial extension and lesion thickness.
Methods
Thirty-two subjects affected by oral cavity carcinoma were prospectively evaluated with intraoral ultrasound. The ultrasound sensitivity, the correlation between the ultrasound level of infiltration, and lesion diameters and thickness were assessed.
Results
A 91% ultrasound sensitivity was found with no significant correlation between tumor diameter and level of histological infiltration (P >.05). A thickness of <2 mm was associated to tumor extension to the lamina propria, a value of >6 mm to muscular layer infiltration. Lymph adenopathies were identified in 21% of cases, associated to muscular layer infiltration in all cases.
Conclusion
In the study of early oral cavity tumors, ultrasound is accurate for demonstrating the level of tumor infiltration and contributes to the therapeutic choice.
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Developing a risk stratification tool for audit of outcome after surgery for head and neck squamous cell carcinoma
Abstract
Background
Patients treated surgically for head and neck squamous cell carcinoma (HNSCC) represent a heterogeneous group. Adjusting for patient case mix and complexity of surgery is essential if reporting outcomes represent surgical performance and quality of care.
Methods
A case note audit totaling 1075 patients receiving 1218 operations done for HNSCC in 4 cancer networks was completed. Logistic regression, decision tree analysis, an artificial neural network, and Naïve Bayes Classifier were used to adjust for patient case-mix using pertinent preoperative variables.
Results
Thirty-day complication rates varied widely (34%-51%; P < .015) between units. The predictive models allowed risk stratification. The artificial neural network demonstrated the best predictive performance (area under the curve [AUC] 0.85).
Conclusion
Early postoperative complications are a measurable outcome that can be used to benchmark surgical performance and quality of care. Surgical outcome reporting in national clinical audits should be taking account of the patient case mix.
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Narrow-band imaging in transoral laser surgery for early glottic cancer in relation to clinical outcome
Abstract
Background
The purpose of this study was to validate the prognostic value of adding narrow-band imaging (NBI) during transoral laser surgery (TLS) for early glottic cancer.
Methods
In 84 patients, 93 transoral laser resections were performed for carcinoma in situ (Tcis), T1, or T2 glottic cancer. TLS was preceded by intraoperative evaluation using traditional white-light imaging (WLI) in 51 cases. In 42 cases, NBI was used in addition to WLI. Local recurrence rate and recurrence-free survival were retrospectively compared between both groups.
Results
Local recurrences developed in 14% of the 93 cases: 12 of 51 patients (24%) were treated by TLS based on WLI alone, and in 1 of 42 patients (2%) in the NBI group (P < .01). Two-year recurrence-free survival was 82% in the WLI group and 98% in the NBI group (P < .05).
Conclusion
Additional use of NBI during TLS for early glottic cancer significantly improves clinical outcome.
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Preoperative vitamin D level as predictor of post-thyroidectomy hypocalcemia in patients sustaining transient parathyroid injury
Abstract
Background
Several studies have sought to identify predictors of postoperative hypocalcemia after total thyroidectomy; however, there have been conflicting results regarding the impact of preoperative vitamin D deficiency.
Methods
The medical records of patients undergoing total thyroidectomy were retrospectively reviewed. The number of parathyroid glands identified or reimplanted at the time of surgery was used as a marker of transient parathyroid gland damage.
Results
Sixty-seven patients were included in the study. Vitamin D deficiency was a significant predictor of hypocalcemia in patients in whom ≥3 parathyroid glands were identified, but not in patients in whom 0-2 parathyroid glands were identified intraoperatively (odds ratio [OR] 5.8; P = .036).
Conclusion
Vitamin D deficiency is a significant predictor of postoperative hypocalcemia in patients in whom ≥3 parathyroid glands are identified intraoperatively, but not in patients who sustain minimal transient damage to the parathyroid glands.
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FDG uptake in cervical lymph nodes in children without head and neck cancer
Abstract
Background
Reactive cervical lymphadenopathy is common in children and may demonstrate increased 18F–fluoro-deoxyglucose (18F–FDG) uptake on positron emission tomography/computed tomography (PET/CT).
Objective
We sought to evaluate the frequency and significance of 18F–FDG uptake by neck lymph nodes in children with no history of head and neck cancer.
Materials and methods
The charts of 244 patients (114 female, mean age: 10.4 years) with a variety of tumors such as lymphoma and post-transplant lymphoproliferative diseases (PTLD), but no head and neck cancers, who had undergone 18F–FDG PET/CT were reviewed retrospectively. Using the maximum standardized uptake value (SUVmax), increased 18F–FDG uptake by neck lymph nodes was recorded and compared with the final diagnosis based on follow-up studies or biopsy results.
Results
Neck lymph node uptake was identified in 70/244 (28.6%) of the patients. In 38 patients, the lymph nodes were benign. In eight patients, the lymph nodes were malignant (seven PTLD and one lymphoma). In 24 patients, we were not able to confirm the final diagnosis. Seven out of the eight malignant lymph nodes were positive for PTLD. The mean SUVmax was significantly higher in malignant lesions (4.2) compared with benign lesions (2.1) (P = 0.00049).
Conclusion
18F–FDG uptake in neck lymph nodes is common in children and is frequently due to reactive lymph nodes, especially when the SUVmax is <3.2. The frequency of malignant cervical lymph nodes is higher in PTLD patients compared with other groups.
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With Omaha couple tested by cancer and fire, family and friends step up to lead home remodel - Omaha World-Herald
Omaha World-Herald |
With Omaha couple tested by cancer and fire, family and friends step up to lead home remodel
Omaha World-Herald “I remember she grabbed a can of whipped cream and sprayed it in her mouth and pushed her tongue up and pushed it through her teeth,” making her 1-year-old niece giggle. The next day, the mood changed when the Chihuahua crawled onto Claudia's ... |
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Early nutrition and ageing: can we intervene?
Abstract
Ageing, a complex process that results in progressive decline in intrinsic physiological function leading to an increase in mortality rate, has been shown to be affected by early life nutrition. Accumulating data from animal and epidemiological studies indicate that exposure to a suboptimal nutritional environment during fetal life can have long-term effects on adult health. In this paper, we discuss the impact of early life nutrition on the development of age-associated diseases and life span. Special emphasis is given to studies that have investigated the molecular mechanisms underlying these effects. These include permanent structural and cellular changes including epigenetics modifications, oxidative stress, DNA damage and telomere shortening. Potential strategies targeting these mechanisms, in order to prevent or alleviate the detrimental effects of suboptimal early nutrition on lifespan and age-related diseases, are also discussed. Although recent reports have already identified effective therapeutic interventions, such as antioxidant supplementation, further understanding of the extent and nature of how early nutrition influences the ageing process will enable the development of novel and more effective approaches to improve health and extend human lifespan in the future.
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Development of an instrument to measure Faculty’s information and communication technology access (FICTA)
Abstract
The phenomenon of “digital divide” is complex and multidimensional, extending beyond issues of physical access. The purpose of this study was to develop a scale to measure a range of factors related to digital divide among higher education faculty and to evaluate its reliability and validity. Faculty’s Information and Communication Technology Access (FICTA) scale was tested and validated with 322 faculty teaching in public and private sector universities. Principal components analysis with varimax rotation confirmed an 8-factor solution corresponding to various dimensions of ICT access. The 57-item FICTA scale demonstrated good psychometric properties and offers researchers a tool to examine faculty’s access to ICT at four levels – motivational, physical, skills, and usage access.
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Programmed Death-1 Pathway in Orbital Invasion of Cutaneous Carcinomas.
Purpose: The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. Methods: Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10). The numbers of positively-staining cells/40x field were counted across 5 consecutive fields, and statistical analyses were performed to compare the differences between the 2 groups. Results: Programmed death-1 receptor positivity was seen in means of 30.9 cells/40x field and 62.4 cells/40x field for nodular basal cell carcinomas and invasive malignancies, respectively (p = 0.0046). A mean of 4.54 cells/40x field stained positively for the programmed death-1 ligand in nodular basal cell carcinoma, whereas a mean of 46.4 cells/40x field stained positively for programmed cell death ligand-1 in orbital invasive cutaneous carcinomas (p = 0.0015). Both of these differences were statistically significant. Conclusions: Both the programmed death-1 receptor and its ligand are enriched in invasive cutaneous malignancies. This finding indicates that negative regulation of the immune system likely prohibits tumor surveillance, and facilitates increasing aggressiveness and invasion of cutaneous malignancies. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
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Conjunctival Inclusion Cyst Containing a Scleral Buckle.
No abstract available
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Enhanced Fasanella-Servat Procedure for the Graded Repair of Blepharoptosis.
Purpose: To describe in detail a technique for a modified Fasanella-Servat procedure that provides a simplified method for graded Mueller muscle excision with minimal and controlled tarsal excision. Methods: A retrospective study of 71 patients (102 eyelids) who underwent the modified Fasanella-Servat procedure is reported. Measurements include the preoperative, post-phenylephrine, and postoperative margin-to-reflex distance-1, and postoperative upper eyelid height symmetry as determined by the absolute difference between right- and left-sided margin-to-reflex distance-1. Postoperative complications are reported. Results: The average increase in margin-to-reflex distance-1 was 2.4 mm with an average postoperative upper eyelid height symmetry of 0.4 mm. Postoperative asymmetry was 1.5 mm or less in 68 patients, a success rate of 96%. Four patients (6%) exhibited overcorrection, 2 of which required additional surgery. No lagophthalmos or notable eyelid contour abnormalities were seen. Conclusions: The modified Fasanella-Servat technique offers a simple method to isolate and resect Mueller muscle and a minimal segment of tarsus in a quantitative fashion, allowing for a graded repair of blepharoptosis and thereby decreasing the risk of postoperative overcorrection, lagophthalmos, and eyelid contour asymmetry whilst preserving the bulk of tarsus. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
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Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual.
Purpose: To determine the prognostic value of the staging criteria for eyelid tumors in the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual and to determine, for each type of eyelid tumor, which AJCC T categories are associated with increased risk of nodal metastasis and thus potential usefulness of sentinel lymph node biopsy. Methods: Systematic review and analysis of articles found by searching PubMed and Google Scholar using the search terms "AJCC," "eyelid," "carcinoma," and "melanoma." Results: Rates of local recurrence, regional nodal metastasis, and distant metastasis were approximately 7% to 10%, 1% to 9%, and 0% to 0.8%, respectively, for eyelid squamous cell carcinoma; 5% to 6%, 8% to 23%, and 2% and 14%, respectively, for eyelid sebaceous carcinoma; 10%, 10% to 22%, and 19% to 22%, respectively, for eyelid Merkel cell carcinoma (when staged according to the criteria for eyelid carcinoma as opposed to Merkel cell carcinoma), 14%, 5%, and 0%, respectively, for eyelid sweat gland carcinoma; and 2%, 9%, and 6%, respectively, for eyelid melanoma. Overall, the risks of local recurrence and regional nodal and distant metastasis appeared to increase with increasing AJCC T category, although not statistically significant in all studies. Clinical T2b or greater T category was significantly associated with increased risk of nodal metastasis for eyelid squamous cell carcinomas, sebaceous carcinomas, Merkel cell carcinomas (staged with eyelid carcinoma criteria), sweat gland carcinomas, and melanomas. Clinical T3 or greater T category was significantly associated with distant metastasis for eyelid carcinomas and melanomas. Conclusion: For eyelid carcinomas and eyelid melanomas, AJCC 7th edition T category correlates with the risks of nodal and distant metastasis, with T2b and larger tumors associated with highest risk of nodal metastasis. Patients with T2b or larger tumors may be candidates for sentinel lymph node biopsy or close nodal surveillance. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
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Spheno-Orbital Meningiomas: An Analysis Based on World Health Organization Classification and Ki-67 Proliferative Index.
Purpose: To evaluate the clinical behavior of spheno-orbital meningiomas with regard to World Health Organization (WHO) tumor grade and Ki-67, a cellular marker of proliferation. Methods: A retrospective review over a 16-year period of the demographic, clinical, radiographic, and surgical data of all patients with spheno-orbital meningioma who underwent surgical resection. Tumor specimens were examined histologically using the current WHO 2016 classification and immunohistochemically using Ki-67/MIB-1 monoclonal antibody. Results: Thirty-eight patients met all inclusion criteria: 78.9% of tumors were WHO grade I with a mean Ki-67 of 3.76, and 93% of patients were clinically stable at last follow up; 10.5% of lesions were WHO grade II (atypical) with a mean Ki-67 of 14.93, and 10.5% of lesions were WHO grade III (anaplastic) with a mean Ki-67 of 58.3. All grade II and III meningiomas exhibited an aggressive clinical course. There were statistically significant correlations between disease clinical progression and WHO tumor grade (p =3.3 correlated with recurrence (p = 0.0256). Overall, disease-specific mortality occurred in 5 (13%) patients. Conclusions: Ki-67 index is a valuable marker to use in conjunction with WHO grade to predict meningioma behavior, particularly in histologically borderline lesions, and possibly to identify a subset of WHO grade I tumors at risk of recurrence. This combination of methods can aid in tailoring treatment and surveillance strategies. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
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Efficient dibutyltin (DBT) elimination by the microscopic fungus Metarhizium robertsii under conditions of intensive aeration and ascorbic acid supplementation
Abstract
Dibutyltin (DBT) is an environmental pollutant characterized by immunotoxic, neurotoxic, and pro-oxidant properties. In this study, an attempt was made to enhance DBT elimination by the Metarhizium robertsii strain. We observed enhanced fungal growth in the bioreactor (pO2 ≥ 20%) compared to flask cultures (μ max increased from 0.061 to 0.086 h−1). Moreover, under aerated conditions, M. robertsii mycelium with “hairy” morphology biodegraded DBT (20 mg l−1) 10-fold faster in the bioreactor than in the flask cultures. Monobutyltin (MBT) and a hydroxylated derivative of MBT (OHBuSnH2) were detected as by-products of dibutyltin debutylation. Simultaneous usage of glucose and butyltins indicates the comatabolic nature of monobutyltin and dibutyltin removal. In order to protect fungal cells from oxidative stress caused by DBT presence, vitamin C (20 mg l−1) was applied. Supplementation with ascorbic acid (AA) resulted in a 3-fold acceleration of MBT removal during the first 7 h of incubation. Using the HPLC-MS/MS technique, a quantitative analysis of malondialdehyde (MDA), a marker of oxidative stress, was performed. In the AA presence, a decrease in the MDA amount (about 45%) was observed compared to the case with fungal cells exposed to DBT alone.
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Expression of the cyanobacterial enzyme cyanase increases cyanate metabolism and cyanate tolerance in Arabidopsis
Abstract
Cyanate and its derivatives are considered as environmental hazardous materials. Cyanate is released to the environment through many chemical industries and mining wastewater. Cyanase enzyme converts cyanate into CO2 and NH3 in a bicarbonate-dependent reaction. At low cyanate concentrations, the endogenous plant cyanases play a vital role in cyanate detoxification. However, such cyanate biodegradation system is probably insufficient due to the excess cyanate concentrations at contaminated sites. In this study, we have transferred the activity of the cyanobacterial cyanase into Arabidopsis thaliana plants in order to enhance plant resistance against cyanate toxicity. The enzyme was shown to be active in planta. Transgenic plants exposed to cyanate, either applied by foliar spray or supplemented in growth medium, showed less reduction in pigment contents, antioxidant enzymes, carbohydrate contents, and reduced levels of plant growth retardation. Plant growth assays under cyanate stress showed enhanced growth and biomass accumulation in cyanase overexpressors compared to control plants. Results of this study provide evidence for developing novel eco-friendly phytoremediation systems for cyanate detoxification.
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Characterization of PM 2.5 chemical composition at the Demokritos suburban station, in Athens Greece. The influence of Saharan dust
Abstract
The aim of this work is to study the atmospheric concentrations of selected major and trace elements and ions found in PM2.5, at a suburban site in Athens, Greece, and discuss on the impact of the different sources. Special focus is given to the influence of Saharan dust episodes. The seasonal variability in the metal and ion concentrations is also examined. The results show that PM2.5 mass concentrations are significantly influenced by Saharan dust events; it is observed that when the PM2.5 concentration is higher than 25 μg/m3, five out of six times, the air mass crossed North Africa at an altitude within the boundary layer. Fe is found to be the element with the more significant seasonal variability, displaying much higher concentrations during cold period. The frequent Saharan dust intrusions in the cold period of this dataset may explain this result. Mineral dust and secondary aerosol are the main PM2.5 components (29 and 34%, respectively). During Saharan dust events, the concentration of mineral dust is increased by 35% compared to the days without dust intrusions, while an increase of 68% of the sea salt is also observed. During event days, PM2.5 concentrations are also increased by 14%. Anthropogenic components do not decrease during those days, while sulfate displays even a slight increase, suggesting enrichment of mineral dust with secondary sulfates. The results indicate that African dust intrusions add a rather significant PM pollution load even in the PM2.5 fraction, with implication to population exposure and human health.
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Tsunami run-up and inundation along the coast of Sabah and Sarawak, Malaysia due to a potential Brunei submarine mass failure
Abstract
Submarine landslides, also known as submarine mass failures (SMFs), are major natural marine disasters that could critically damage coastal facilities such as nuclear power plants and oil and gas platforms. It is therefore essential to investigate submarine landslides for potential tsunami hazard assessment. Three-dimensional seismic data from offshore Brunei have revealed a giant seabed mass deposited by a previous SMF. The submarine mass extends over 120 km from the continental slope of the Baram Canyon at 200 m water depth to the deep basin floor of the Northwest Borneo Trough. A suite of in-house two-dimensional depth-averaged tsunami simulation model TUNA (Tsunami-tracking Utilities and Application) is developed to assess the vulnerability of coastal communities in Sabah and Sarawak subject to potential SMF tsunami. The submarine slide is modeled as a rigid body moving along a planar slope with the center of mass motion parallel to the planar slope and subject to external forces due to added mass, gravity, and dissipation. The nonlinear shallow water equations are utilized to simulate tsunami propagation from deepwater up to the shallow offshore areas. A wetting-drying algorithm is used when a tsunami wave reaches the shoreline to compute run up of tsunami along the shoreline. Run-up wave height and inundation maps are provided for seven densely populated locations in Sabah and Sarawak to highlight potential risks at each location, subject to two scenarios of slide slopes: 2° and 4°. The first wave may arrive at Kudat as early as 0.4 h after the SMF, giving local communities little time to evacuate. Over a small area, maximum inundated depths reaching 20.3 m at Kudat, 26.1 m at Kota Kinabalu, and 15.5 m at Miri are projected, while the maximum inundation distance of 4.86 km is expected at Miri due to its low-lying coast. In view of the vulnerability of some locations to the SMF tsunami, it is important to develop and implement community resilience program to reduce the potential damage that could be inflicted by SMF tsunamis.
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Characterization of polycyclic aromatic hydrocarbons in soil close to secondary copper and aluminum smelters
Abstract
A total of 35 surface soil samples around two secondary copper smelters and one secondary aluminum smelter were collected and analyzed for 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs). The concentrations of PAHs were highest when the soil sample sites were closest to the secondary copper smelters. And, a level gradient of PAHs was observed in soil samples according to the distance from two secondary copper smelters, respectively. The results suggested that PAH concentrations in surrounding soils may be influenced by secondary copper smelters investigated, whereas no such gradient was observed in soils around the secondary aluminum smelter. Further analysis revealed that PAH patterns in soil samples also showed some difference between secondary copper and aluminum smelter, which may be attributed to the difference in their fuel and smelting process. PAH patterns and diagnostic ratios indicated that biomass burning may be also an important source of PAHs in the surrounding soil in addition to the emissions from the plants investigated.
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Heavy metals bioconcentration from soil to vegetables and appraisal of health risk in Koka and Wonji farms, Ethiopia
Abstract
Heavy metal accumulation in agricultural crops has grown a major concern globally as a result of a significant health impact on human. The quantification of heavy metals (Cd, Pb, Cr, Zn, Cu, and Ni) in the soil and vegetables at two sites (Koka and Wonji Gefersa) was done using flame atomic absorption spectrophotometer. The mean concentrations of heavy metals in vegetable fields’ soil samples obtained from Koka were higher for Pb, Cr, Zn, Cu, and Ni. The overall results of soil samples ranged 0.52–0.93, 13.6–27.3, 10.0–21.8, 44.4–88.5, 11.9–30.3, and 14.7–34.5 mg kg−1 for Cd, Pb, Cr, Zn, Cu, and Ni, respectively. The concentrations of heavy metals were maximum for Cd (0.41 ± 0.03 mg kg−1), Pb (0.54 ± 0.11 mg kg−1), Zn (14.4 ± 0.72 mg kg−1), Cu (2.84 ± 0.27 mg kg−1), and Ni (1.09 ± 0.11 mg kg−1) in Cabbage and for Cr (2.63 ± 0.11 mg kg−1) in green pepper. The result indicated that Cd has high transfer factor value and Pb was the lowest. The transfer pattern for heavy metals in different vegetables showed a trend in the order: Cd > Zn > Cu > Cr > Ni > Pb. Among different vegetables, cabbage showed the highest value of metal pollution index and bean had the lowest value. Hazard index of all the vegetables was less than unity; thus, the consumption of these vegetables is unlikely to pose health risks to the target population.
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Quantitative characterization of pore structure of several biochars with 3D imaging
Abstract
Pore space characteristics of biochars may vary depending on the used raw material and processing technology. Pore structure has significant effects on the water retention properties of biochar amended soils. In this work, several biochars were characterized with three-dimensional imaging and image analysis. X-ray computed microtomography was used to image biochars at resolution of 1.14 μm and the obtained images were analysed for porosity, pore size distribution, specific surface area and structural anisotropy. In addition, random walk simulations were used to relate structural anisotropy to diffusive transport. Image analysis showed that considerable part of the biochar volume consist of pores in size range relevant to hydrological processes and storage of plant available water. Porosity and pore size distribution were found to depend on the biochar type and the structural anisotopy analysis showed that used raw material considerably affects the pore characteristics at micrometre scale. Therefore, attention should be paid to raw material selection and quality in applications requiring optimized pore structure.
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An anoxic-aerobic system for simultaneous biodegradation of phenol and ammonia in a sequencing batch reactor
Abstract
A laboratory-scale sequencing batch reactor (SBR) was investigated to treat artificial pretreated coal gasification wastewater that was mainly contained of ammonia and phenol. The efficiency of SBR fed with increasing phenol concentrations (from 150 to 300 mg l−1) and the relationship among phenol, nitrogen removal, and the microbial community structure were evaluated. When the phenol feeding concentration was increased to about 300 mg l−1, the removal efficiency was above 99.0%, demonstrating the robustness of phenol removal capacity. The study showed that most phenol was degraded in anoxic stage. The average removal efficiencies of ammonia and total nitrogen were 98.4 and 81.9%, respectively, with average NH4+-N concentration of 107.5 mg l−1 and COD/N 7.5. Low temperature caused sludge loss that led to the decreased performance. Increasing the temperature could not recover the performance effectively. The data from bacterial analysis revealed that Delftia, Hydrogenophaga, and unclassified Xanthomonadaceae played a significant role in phenol degradation before the temperature increase, while uncultured Syntrophococcus sp. and unclassified Rhodocyclaceae were responsible for phenol degradation after the temperature increase. These results imply that the SBR holds potential for the simultaneous removal of phenolic compounds and nitrogen through aerobic ammonia oxidation and anoxic denitrification with phenol as the co-organic carbon source.
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Remediation of PCB-contaminated soil using a combination of mechanochemical method and thermal desorption
Abstract
The combination of mechanochemical method and thermal desorption for remediating polychlorinated biphenyls (PCBs) in contaminated soil was tested in this study. The effects of grinding time and heating time on PCB removal efficiency were investigated. The contaminated soil, mixed with CaO powder at a weight ratio of 1:1, was first ground using a planetary ball mill. After 4 h of grinding, the total PCB concentration and its toxic equivalence quantity (TEQ) decreased by 74.6 and 75.8%, respectively. Then, after being heated at 500 °C for 60 min, the residual PCBs in mechanochemical + thermal treated soil decreased to 247 ng/g, resulting in a removal efficiency of 99.95%. The removal effect can be promoted by longer grinding time and heating time; however, increased energy consumption was inevitable. The combination of grinding time and heating time should be optimized in a practical remediation process.
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Erratum to: Isotherm, kinetic, and thermodynamic study of ciprofloxacin sorption on sediments
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Study of plasma off-gas treatment from spent ion exchange resin pyrolysis
Abstract
Polystyrene divinylbenzene-based ion exchange resins are employed extensively within nuclear power plants (NPPs) and research reactors for purification and chemical control of the cooling water system. To maintain the highest possible water quality, the resins are regularly replaced as they become contaminated with a range of isotopes derived from compromised fuel elements as well as corrosion and activation products including 14C, 60Co, 90Sr, 129I, and 137Cs. Such spent resins constitute a major proportion (in volume terms) of the solid radioactive waste generated by the nuclear industry. Several treatment and conditioning techniques have been developed with a view toward reducing the spent resin volume and generating a stable waste product suitable for long-term storage and disposal. Between them, pyrolysis emerges as an attractive option. Previous work of our group suggests that the pyrolysis treatment of the resins at low temperatures between 300 and 350 °C resulted in a stable waste product with a significant volume reduction (>50%) and characteristics suitable for long-term storage and/or disposal. However, another important issue to take into account is the complexity of the off-gas generated during the process and the different technical alternatives for its conditioning. Ongoing work addresses the characterization of the ion exchange resin treatment’s off-gas. Additionally, the application of plasma technology for the treatment of the off-gas current was studied as an alternative to more conventional processes utilizing oil- or gas-fired post-combustion chambers operating at temperatures in excess of 1000 °C. A laboratory-scale flow reactor, using inductively coupled plasma, operating under sub-atmospheric conditions was developed. Fundamental experiments using model compounds have been performed, demonstrating a high destruction and removal ratio (>99.99%) for different reaction media, at low reactor temperatures and moderate power consumption. The role of H2O as an important participant of the oxidation mechanisms in plasma conditions was established. The combination of both processes could represent a simple, safe, and effective alternative for treating spent ion exchange resins with a large reduction of generated gaseous byproducts in fuel cycle facilities where processes that utilize open flames are undesirable.
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Magnificent Mount St. Helens Photos, Part 7
-- Read more on ScientificAmerican.com
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Arriva in Italia il primo vaccino anti Hpv 9-valente - La Repubblica
L'ultima Ribattuta |
Arriva in Italia il primo vaccino anti Hpv 9-valente
La Repubblica Protegge contro nove tipi di papillomavirus (Hpv), riuscendo a prevenire fino al 90% dei tumori del collo dell'utero. E' il nuovo vaccino 9-valente finalmente disponibile anche in Italia e indicato in adolescenti maschi e femmine a partire dai 9 anni ... Papillomavirus: vaccino anti HPV 9-valenteBlasting News Hpv, arriva in Italia il vaccino efficace contro 9 tipi di papillomavirusL'ultima Ribattuta Hpv, arriva in Italia il nuovo vaccino più efficace Protegge contro nove tipi di papillomavirusSi24 - Il vostro sito quotidiano all 27 news articles » |
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Perugia, intervento chirurgico da “mission (quasi) impossible” - Umbria Journal il sito degli umbri
Umbria Journal il sito degli umbri |
Perugia, intervento chirurgico da “mission (quasi) impossible”
Umbria Journal il sito degli umbri Perugia, intervento chirurgico da “mission (quasi) impossible” PERUGIA – Aveva in bocca, vicino alle tonsille, un tumore grande come un mandarino. Che ormai ... and more » |
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Thyroid cancer: treatment and prognosis - Medical Xpress - Medical Xpress
Thyroid cancer: treatment and prognosis - Medical Xpress
Medical Xpress Dear Mayo Clinic: How is thyroid cancer treated? Does it always require taking out the thyroid? When is iodine treatment used, and how does that work? and more » |
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Atlantic Health System Appoints National Leader in Head and Neck Cancer Surgery to Medical Director, Head & Neck ... - TAPinto.net
TAPinto.net |
Atlantic Health System Appoints National Leader in Head and Neck Cancer Surgery to Medical Director, Head & Neck ...
TAPinto.net ... Leonard B. Kahn Head & Neck Cancer Institute evaluate and treat the entire spectrum of head and neck cancers, from early stage to the most complex advanced cancers of the throat, voice box, salivary glands, thyroid gland, mouth, lips, nose, and ... and more » |
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hOCT1 gene expression predict for optimal response to Imatinib in Tunisian patients with chronic myeloid leukemia
Abstract
Purpose
Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients.
Methods
hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7.
Results
Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V>M (g.1222G>A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3′ end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients.
Conclusions
hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.
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Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38
Abstract
Purpose
Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38.
Methods
Uptake of SN-38 by OATP1B1 was evaluated using cells stably expressing OATP1B1. Serum was obtained from > 400 ESKD patients undergoing hemodialysis. Deproteinized serum was combined with human serum albumin (HSA) to explore the effects of albumin-bound and unbound serum compounds.
Results
Uptake clearance of SN-38 in OATP1B1 cells decreased by 40% in the presence of uremic serum residue with albumin compared to that in the presence of normal serum residue. Additional UTs (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) combined with normal serum residue in HSA decreased OATP1B1-mediated SN-38 transport by 32.1% compared to that in the presence of normal serum residue. The inhibitory effect of albumin-unbound fraction with UTs and normal serum residue was comparable to that of uremic serum residue, with an uptake decrease of 17.2% compared to that reported in the presence of normal serum residue.
Conclusions
Hepatic uptake of SN-38 via OATP1B1 decreases in ESKD patients through cooperative inhibitory effects of UTs and serum components.
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A phase II study of REOLYSIN ® (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma
Abstract
REOLYSIN® (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN® on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN®. Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN® in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN®, including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN® combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN® with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.
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Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041)
Abstract
Purpose
This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.
Methods
Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review.
Results
Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3–5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3–5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3–43.5) for cutaneous melanoma and 25.0% (95% CI 3.2–65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma.
Conclusion
The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.
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Inhibition of GOT1 sensitizes colorectal cancer cells to 5-fluorouracil
Abstract
Purpose
Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined.
Methods
HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1. Following 5-FU treatment, cellular proliferation was evaluated, the NADP+/NADPH ratio was monitored, ROS was measured, and intracellular levels of glutamine (Gln), Aspartate (Asp), oxaloacetate (OAA), malate, and pyruvate were investigated using liquid chromatography–mass spectrometry (LC-MS). A CRC subcutaneous tumor model was performed to determine the impact of GOT1 inhibition on 5-FU efficacy in vivo.
Results
In response to 5-FU administration, CRC cells undergo metabolic adaptation, resulting in increased glutamine flux for the synthesis of aspartate. GOT1 is responsible for the conversion of glutamine-derived aspartate into OAA, which subsequently can be converted into malate and pyruvate. The GOT1-mediated metabolic process is able to maintain the NADP+/NADPH ratio, which counteracts 5-FU-induced oxidative stress. Inhibition of GOT1 impaired the defense against 5-FU-induced ROS, thereby sensitizing cells to 5-FU. The importance of GOT1 in supporting tumor growth during 5-FU treatment was also indicated in an in vivo tumor model of CRC.
Conclusion
These findings show that GOT1 could serve as a promising target for increasing the anticancer efficacy of the conventional therapy in patients with CRC.
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The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2
Abstract
Purpose
Hepatocellular carcinoma (HCC) is a common digestive system malignancy that is associated with a poor prognosis. This study researched the interaction of tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) in HCC cells proliferation, migration and invasion and examined their influence on the expression of G protein-coupled receptor kinase 2 (GRK2) and relevant receptors.
Methods
Cell Counting Kit-8 and Transwell assays were performed to evaluate the effects of TNF-α and Ang II on HepG2 cells proliferation, migration and invasion. Flow cytometry was used to investigate the expression of tumor necrosis factor receptor 1 (TNFR1), angiotensin II type 1 (AT1R) and type 2 receptors (AT2R) on the surface of HepG2 cells. Additionally, Western blot was performed to assess the modulation of GRK2 expression by TNF-α and Ang II in HepG2 cells. Meanwhile, GRK2 siRNA-transfected HepG2 cells were used to confirm the effects of GRK2, TNF-α and Ang II on the proliferation, migration and invasion of GRK2-knockdown HCC cells. Finally, the expression of TNF-α, Ang II, TNFR1, AT1R, AT2R and GRK2 proteins in HCC, tumor-adjacent and normal liver tissues were tested by immunohistochemistry.
Results
The data demonstrated that TNF-α and Ang II can enhance the proliferation, migration and invasion of HepG2 cells through suppressing GRK2 expression but that the two reagents combined did not have synergistic effects. Moreover,overexpression of TNFR1 and AT1R perhaps promoted the formation and progression of HCC, while high AT2R expression had the opposite effect.
Conclusions
This study provides new ideas for the prevention and treatment of HCC by researching the interaction and probable mechanism of different bioactive factors associated with HCC.
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Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study
Abstract
Objectives
We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma.
Methods
At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography. All enrolled patients were genotyped for ABCB1 (rs2032582; rs1045642) and ABCG2 (rs2231137; rs2231142; rs2622604) by blood genomic DNA extraction and Mass ARRAY genotyping. The clinical response was evaluated after 3months of treatment according to the RECIST criteria.
Key findings
Significant associations between sorafenib exposure and the studied polymorphisms were observed for ABCB1 3435C>T, ABCG2 34G>A, ABCG2 1143C>T and ABCG2 421C>A, but not for ABCB1 2677G>TA SNP. In heterozygous patients for ABCB1 3435 C>T, ABCG2 34 G>A and ABCG2 1143 C>T polymorphisms were significantly associated with the lowest sorafenib plasma levels. Those patients presented a tendency to have the best clinical evolution.
Conclusion
Heterozygous forms of the studied polymorphisms could be associated with a better therapeutic response.
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An apparent clinical pharmacokinetic drug–drug interaction between bevacizumab and the anti-placental growth factor monoclonal antibody RO5323441 via a target-trapping mechanism
Abstract
Purpose
RO5323441 is a humanized anti-placental growth factor (PlGF) monoclonal antibody that has shown preclinical activity in several cancer models. The objective of this analysis is to examine the pharmacokinetic (PK) results from four Phase I studies that have been conducted with RO5323441 (n = 61) and to report an apparent drug–drug interaction observed when RO5323441 was administered in combination with bevacizumab.
Methods
The four Phase I studies were a multiple-ascending dose study in 23 patients with solid tumors (Study 1), an open-label study in seven patients with colorectal/ovarian cancer (Study 2), a sorafenib combination study in nine patients with hepatocellular carcinoma (Study 3), and a bevacizumab combination study in 22 patients with recurrent glioblastoma (Study 4). A two-compartment linear population PK model was developed from these four studies to characterize the PK of RO5323441 in patients with cancer.
Results
The PK properties of RO5323441 were similar in the first three studies. However, substantially higher RO5323441 exposures were observed in Study 4 when RO5323441 was administered in combination with bevacizumab. A linear two-compartmental population PK model indicated that the co-administration of bevacizumab would decrease the clearance of RO5323441 by 53%. Clinical data suggested that the decrease in RO5323441 clearance was inversely associated with bevacizumab exposure.
Conclusions
The exact reason for the increase in RO5323441 exposure following bevacizumab co-administration is not currently known. One possibility is a drug–drug interaction via a target-trapping mechanism that is mediated by the vascular endothelial growth factor receptor-1 (VEGFR-1).
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Pemetrexed monotherapy for chemo-naïve elderly (aged ≥80) patients with non-squamous non-small cell lung cancer: results from combined analysis of two single arm phase II studies (HANSHIN002 and 003)
Abstract
Purpose
The aim of this retrospective study was to evaluate via combined analysis the efficacy and safety of pemetrexed monotherapy for chemo-naïve elderly patients aged ≥80 with non-squamous non-small cell lung cancer (NSCLC).
Methods
We conducted a combined analysis from two phase II studies of pemetrexed for chemo-naïve elderly (aged ≥75) (n = 47) and performance status 2 (n = 28) patients with advanced non-squamous NSCLC. Population aged ≥80 (80+ Group) was compared to those aged 70–79 (70’s Group).
Results
We analyzed a total of 66 patients (37 70s and 29 80+ Groups) after exclusion of 4 ineligible and 5 aged ≤69 patients. Overall response rate, disease control rate, median progression-free survival, and median overall survival of 70s vs. 80+ Groups were 13.5 vs. 13.8% [p = not significant (NS)], 67.6 vs. 58.6% (p = 0.608), 3.7 months vs. 4.2 months (p = 0.5588) and 18.5 vs. 13.5 months (p = 0.2621), respectively. Non-hematological and hematological toxicities ≥grade 3 of 70s vs. 80+ Groups were 24 vs. 35% (p = 0.4192) and 49 vs. 52% (p = NS), respectively. Dose reduction and/or delay due to toxicities of 70s vs. 80+ Groups was 19 vs. 28% (p = 0.7784). Febrile neutropenia and interstitial lung disease were not observed. Treatment-related death (bacterial pneumonia) was confirmed in one (3%) of 29 80+ Group patients.
Conclusions
Pemetrexed monotherapy demonstrated similar efficacy and safety between aged ≥80 and aged 70–79 populations. It could be a therapeutic option in clinical practice for elderly non-squamous NSCLC patients aged ≥80 without indications of carboplatin-based combination regimens or docetaxel monotherapy.
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Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect
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Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease
Abstract
Purpose
Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.
Methods
We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.
Results
EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.
Conclusions
EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.
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A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma
Abstract
Purpose
To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC).
Methods
Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m2, day 1), nab-paclitaxel (mg/m2, day 1), and S-1 (mg/day, days 1–7) were 800/100/60–100 at level 1, and 1000/125/60–100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630).
Results
We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients.
Conclusion
In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m2, gemcitabine: 1000 mg/m2 on day 1, S-1: <1.25 m2, 60 mg; 1.25–1.5 m2, 80 mg; >1.5 m2, 100 mg twice a day on days 1–7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.
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XPG genetic polymorphisms and clinical outcome of patients with advanced non-small cell lung cancer under platinum-based treatment: a meta-analysis of 12 studies
Abstract
Purpose
A number of studies on the relationship between xeroderma pigmentosum group G (XPG) polymorphisms and clinical outcomes in non-small cell cancer (NSCLC) have led to inconclusive results. This meta-analysis evaluates the predictive value of XPG polymorphisms on the treatment response rate and overall survival of patients with NSCLC.
Methods
To measure the correlative strength of the relationship between XPG polymorphisms and outcomes of patients with NSCLC, we searched electronic databases, including PubMed and China National Knowledge Infrastructure, to retrieve studies up to August 2016. We also employed pooled odds ratios (ORs) and hazard ratios (HRs) corresponding to 95% confidence intervals (95% CIs).
Results
Twelve studies involving 2877 patients with NSCLC were included: 8 studies involving 1473 patients examined the correlation between XPG polymorphisms and tumor response rate and 7 studies involving 2329 patients reported on the correlation of XPG polymorphisms with overall survival. None of the XPG His1104Asp(C>G)/His46His(C>T) polymorphisms exhibited a correlation with treatment response rate or overall survival. However, in a further stratified analysis by ethnicity, carriers of the 1104G allele were associated with good response among Asians in the homozygote model (GG vs. CC: OR = 1.57, 95% CI: 1.05–2.34, P = 0.027). Meanwhile, further stratified by ethnicity, His46His polymorphism was not associated with RR and OS in any genetic models.
Conclusions
No strong evidence was found to support the use of XPG polymorphisms as tumor response and prognostic factors of patients with NSCLC receiving a platinum-based treatment regimen, which is attributed to marginal association. Studies with large-scale and multiple ethnicities need to be conducted to verify the conclusion.
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Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients
Abstract
Purpose
A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients.
Methods
Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase.
Results
N = 38 patients were randomized to two treatment sequences S1 and S2. PK parameters t 1/2, CL/f, and V z/f were within the same range for the two formulations. Tablet had bioavailability comparable to capsule based on the analysis of AUC0–t, however, tablet administration resulted in an increase of ~25% in C max versus capsule. Common predicted adverse events of pimasertib included ocular events, diarrhea and creatine phosphokinase elevation. Disease control rate was ~29% with 1 partial response and 4 of 10 patients with stable disease >4 months.
Conclusions
Pimasertib tablet was overall well tolerated, had a similar safety and efficacy profile to standard capsule formulation and had bioavailability comparable to capsule.
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A phase 1 study of anti-TGFβ receptor type-II monoclonal antibody LY3022859 in patients with advanced solid tumors
Abstract
Purpose
LY3022859 is an anti-TGFβRII IgG1 monoclonal antibody that inhibits receptor-mediated signaling activation. The primary objective of this phase I study was to determine a phase II dose in patients with advanced solid tumors. Secondary objectives were to assess safety and pharmacokinetics (PK).
Methods
LY3022859 was infused intravenously (IV) at 1.25 mg/kg over 1 h every 2 weeks (Q2W) (cohort 1A) and at flat doses of 12.5 mg (cohort 1B) and 25 mg (cohort 2) over 3 h Q2W.
Results
Fourteen patients were enrolled in cohorts 1A (n = 2), 1B (n = 5), and 2 (n = 7). DLTs were experienced by both patients in cohort 1A (infusion-related reaction) and 2 patients in cohort 2 (cytokine release syndrome and infusion-related reaction). No MTD was determined. At the 25 mg dose level (cohort 2), after fifth infusion, LY3022859 had a short t1/2 (4.37-7.80 h) and rapid clearance (CLss, 0.412 L/h). Exposure increased twofold (from 28.5 to 60.2 μg·h/mL) with increase in dose from 12.5 to 25 mg. No accumulation was observed after repeat administration.
Conclusions
The MTD for LY3022859 was not determined. Dose escalation beyond 25 mg was considered unsafe due to worsening symptoms (uncontrolled cytokine release) despite prophylaxis (corticosteroids and antihistamines).
Trial registration
clinicaltrials.gov Identifier: NCT01646203.
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Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review
Abstract
Purpose
Gene therapy has shown extensive potential to treat human diseases occurring from the defection of genes like various types of cancers. The cationic polymers, as non-viral gene carriers, offer the ability to engineer carrier systems having customized features that can be adapted to suit any system. Upon polymeric micelle systems’ core–shell structure, micelles can create the capacity to load genes/gene-drugs into the different micelle compartments, respectively.
Methods
The search will be managed in Pubmed, Medline, Cochrane library, Embase and Proquest for articles related to polymeric micelle-based gene delivery in order to cancer gene therapy using the accommodative search terms. A database of the first search of all search engines results will be made and repeated articles will be removed. After that, the related articles will be selected, and also the references of selected articles will be searched in order to find any other articles to complete the search database.
Results
This study reviews kinds of polymeric nanomicelles, which have been used in gene therapy, critical parameters for micelle-based gene delivery, challenges and advantages/disadvantages as well as biosafety of nanomicelles in gene delivery systems. Furthermore, the discussion has focused on stimuli-responsive polymers and strategy and mechanisms regarding tumor-selective gene delivery.
Conclusions
This study provides an overview of the advantages/disadvantages of polymeric-based nanocarriers for cancer gene therapy.
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The role of circulating tumor cells in evaluation of prognosis and treatment response in advanced non-small-cell lung cancer
Abstract
Purpose
Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC.
Patients and methods
In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy. CTCs took in peripheral blood were measured by Cell Search detect technique.
Results
Carcino-embryonic antigen and count of metastatic sites were positively related to CTC count analyzed by multiple linear regression (P < 0.05). The median overall survival was 11.2 months (95% CI: 10.37–12.03 months) for the baseline CTC ≥ 2 group compared with 8.3 months (95% CI: 7.72–8.88 months) for the CTC < 2 group (log-rank test P < 0.05). Similarly, patients with CTC ≥ 2 at baseline had a significantly shorter median PFS (4.3 months, 95% CI: 3.7–4.9 months) compared with patients with CTC < 2 (6.2 months, 95% CI: 5.59–6.82 months) (log-rank test P < 0.05). For the disease control (stable disease, partial response, or complete response), group CTC value before treatment did not present difference with that after therapy compared by pared-samples T test (t = 1.455, P = 0.154), similar to the result of progressed group (progressive disease) (t = −0.987, P = 0.335). The CTC value of progressed group was higher than that of disease control group either at baseline or post chemotherapy.
Conclusion
These data provide an evidence of positive correlation between CTC counts with CEA, as well as count of metastatic sites. Meanwhile, CTCs could be an effective predictor of distant metastasis and poor prognosis. In this study, CTCs are poorly related to treatment response. Whether CTCs could be a predictor of curative effect in advanced NSCLC should be validated by more researches in the future.
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In vitro and in vivo evaluation of dasatinib and imatinib on physiological parameters of pulmonary arterial hypertension
Abstract
Purpose
Pulmonary arterial hypertension (PAH) results from occlusion or vasoconstriction of pulmonary vessels, leading to progressive right ventricular failure. Dasatinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia, has been associated with PAH. In contrast, the BCR-ABL1 TKI imatinib has demonstrated anti-vasoproliferative properties and has been investigated as a potential treatment for PAH. Here we describe studies evaluating the effects of dasatinib and imatinib on cardiovascular and pulmonary functions to understand the reported differential consequences of the two TKIs in a clinical setting.
Methods
The direct effects of dasatinib and imatinib were explored in vivo to investigate possible mechanisms of dasatinib-induced PAH. In addition, effects of dasatinib and imatinib on PAH-related mediators were evaluated in vitro.
Results
In rats, both TKIs increased plasma nitric oxide (NO), did not induce PAH-related structural or molecular changes in PA or lungs, and did not alter hemodynamic lung function compared with positive controls. Similarly, in the pulmonary artery endothelial cells and smooth muscle cells co-culture model, imatinib and dasatinib increased NO and decreased endothelin-1 protein and mRNA.
Conclusions
The results of these studies indicated that dasatinib did not induce physiological changes or molecular signatures consistent with PAH when compared to positive controls. Instead, dasatinib induced changes consistent with imatinib. Both dasatinib and imatinib induced biochemical and structural changes consistent with a protective effect for PAH. These data suggest that other factors of unclear etiology contributed to the development of PAH in patients treated with dasatinib.
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Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia
Abstract
Purpose
The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.
Methods
Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients’ characteristics or not.
Results
We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.
Conclusions
The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.
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Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact
Abstract
Purpose
The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy.
Methods
Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses.
Results
Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis.
Conclusions
Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.
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Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis.
Purpose of review: Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. Recent findings: While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFc[gamma]R genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures. Summary: Natural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Cohort study of oncologic emergencies in patients with head and neck cancer.
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Cohort study of oncologic emergencies in patients with head and neck cancer.
Head Neck. 2017 Mar 27;:
Authors: Reyes-Gibby CC, Melkonian SC, Hanna EY, Yeung SJ, Lu C, Chambers MS, Banala SR, Gunn GB, Shete SS
Abstract
BACKGROUND: Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation.
METHODS: We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time.
RESULTS: History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations.
CONCLUSION: Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.
PMID: 28346771 [PubMed - as supplied by publisher]
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Comparison of the safety of electrotome, Harmonic scalpel, and LigaSure for management of thyroid surgery.
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Comparison of the safety of electrotome, Harmonic scalpel, and LigaSure for management of thyroid surgery.
Head Neck. 2017 Mar 27;:
Authors: Yang X, Cao J, Yan Y, Liu F, Li T, Han L, Ye C, Zheng S, Wang S, Ye Y, Jiang K
Abstract
BACKGROUND: Energy-based surgical devices, including electrotome, the Harmonic scalpel, and LigaSure, have been widely applied in thyroid surgery, although a comparison of their safety and efficacy has not been reported yet. In this study, we investigated the feasibility of using hemostatic energy-based surgical devices during thyroid surgery in a canine model.
METHODS: Twenty-four beagle dogs were randomly divided into the following groups: electrotome (30 kW), electrotome (15 kW), the Harmonic scalpel (output level 3), and LigaSure (middle gear). The hemostatic devices were applied on the thyroid surface for 3 seconds and then near the recurrent laryngeal nerve (RLN; distance of 5 mm, 3 mm, or 1 mm) for 3 seconds. Evoked electromyography (EMG) amplitudes were recorded by intraoperative neuromonitoring (IONM). Acute microstructural morphological damage to thyroid tissues and the RLN were evaluated immediately after the procedure by light and electron microscopy.
RESULTS: Electrotome caused a significant decrease in evoked EMG amplitudes when applied at a vertical distance of 1 mm from the RLN, both at 30 kW (1046 ± 404.3 μV vs 153 ± 245.5 μV; p < .001) and 15 kW (1197 ± 589.2 μV vs 986.3 ± 797.3 μV; p = .037), compared with those evoked under normal conditions. Furthermore, distinct acute microstructural morphological changes of the RLNs were observed by light and electron microscopy. However, no significant functional or histological changes were induced by the electrotome at a vertical distance of 5 mm or 3 mm from the RLN. The Harmonic scalpel and LigaSure induced neither marked changes in evoked EMG amplitudes when applied at vertical distances of 5 mm, 3 mm, or 1 mm (all p > .05) nor microstructural morphological changes in the RLNs. The electrotome (15 kW) caused more serious thermal damage to thyroid tissues than that caused by either the Harmonic scalpel or LigaSure (thermal damaged depth: 0.951 ± 0.061 vs 0.756 ± 0.074, p < .001; 0.951 ± 0.061 vs 0.724 ± 0.116, p < .001). Nevertheless, there were no differences between the Harmonic scalpel and LigaSure groups (p = .435).
CONCLUSION: LigaSure and the Harmonic scalpel might be safer than electrotome when used in thyroid operations. LigaSure generates less heat than the Harmonic scalpel and electrotome. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.
PMID: 28346729 [PubMed - as supplied by publisher]
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Synthetic β-nitrostyrene derivative CYT-Rx20 as inhibitor of oral cancer cell proliferation and tumor growth through glutathione suppression and reactive oxygen species induction.
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Synthetic β-nitrostyrene derivative CYT-Rx20 as inhibitor of oral cancer cell proliferation and tumor growth through glutathione suppression and reactive oxygen species induction.
Head Neck. 2017 Mar 27;:
Authors: Wang YY, Chen YK, Hsu YL, Chiu WC, Tsai CH, Hu SC, Hsieh PW, Yuan SF
Abstract
BACKGROUND: The β-nitrostyrene family possesses anticancer properties. In this study, β-nitrostyrene derivative CYT-Rx20 (3'-hydroxy-4'-methoxy-β-methyl-β-nitrostyrene) was synthesized and investigated its anticancer activity in oral cancer.
METHODS: Anticancer activity of CYT-Rx20 and the underlying mechanisms were analyzed using cell viability assay, reactive oxygen species (ROS) generation assay, fluorescence-activated cell sorter analysis, annexin V staining, comet assay, glutathione (GSH)/glutathione disulfide (GSSG) ratio, immunoblotting, soft agar assay, nude mice xenograft study, and immunohistochemistry.
RESULTS: CYT-Rx20-induced cell apoptosis via ROS generation and mitochondrial membrane potential reduction, associated with release of mitochondrial cytochrome C to cytosol and activation of downstream caspases and poly ADP-ribose polymerase (PARP). Furthermore, CYT-Rx20 induced mitochondrial ROS accumulation and mitochondrial dysfunction, followed by GSH downregulation. CYT-Rx20-induced cell apoptosis, ROS generation, and DNA damage were reversed by thiol antioxidants. In nude mice, CYT-Rx20 inhibited oral tumor growth accompanied by increased expression of γH2AX, GSH reductase, and cleaved-caspase-3.
CONCLUSION: CYT-Rx20 has the potential to be further developed into an antioral cancer drug clinically. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.
PMID: 28346709 [PubMed - as supplied by publisher]
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7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.
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7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.
Cancer. 2017 Mar 27;:
Authors: Sun B, Brooks ED, Komaki RU, Liao Z, Jeter MD, McAleer MF, Allen PK, Balter PA, Welsh JD, O'Reilly MS, Gomez D, Hahn SM, Roth JA, Mehran RJ, Heymach JV, Chang JY
Abstract
BACKGROUND: The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system.
METHODS: Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter.
RESULTS: A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]).
CONCLUSIONS: With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in patients with clinical stage I NSCLC. Regional disease recurrence and distant metastases were the dominant manifestations of failure. Surveillance for second primary lung carcinoma is recommended. Cancer 2017. © 2017 American Cancer Society.
PMID: 28346656 [PubMed - as supplied by publisher]
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Glomus jugulare manifesting as angiogenesis of the external ear canal.
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Glomus jugulare manifesting as angiogenesis of the external ear canal.
Ear Nose Throat J. 2017 Mar;96(3):E39-E40
Authors: Chung SY, Liu JK, Park RC, Jyung RW
PMID: 28346654 [PubMed - in process]
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