Tyrosine kinase inhibitors for the therapy of anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is often incurable so new therapeutic approaches are needed. Tyrosine kinases inhibitors (such as imanitib, sunitinib or sorafenib) are under evaluation for the treatment of ATC. Other vascular disrupting agents, such as combretastatin A4 phosphate, and antiangiogenic agents, such as aplidin, PTK787/ZK222584 and human VEGF monoclonal antibodies (bevacizumab, cetuximab), have been evaluated. Small-molecule adenosine triphosphate competitive inhibitors directed intracellularly at EGFRs tyrosine kinase, such as erlotinib or gefitinib, are also studied. Furthermore, new molecules have been shown to be active against ATC, such as CLM94 and CLM3. However, more research is needed to finally identify therapies able to control and to cure this disease

Soluble and cell-associated transferrin receptor in lung cancer.

The expression of transferrin receptor (TfR) has been identified in many malignant tumours. In lung cancer, lymphoma and breast cancer, it has been shown that the expression of TfR correlates with tumour differentiation, probably implying some prognostic value. A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs. Based on these data we examined the utility of measuring sTfR in the serum and bronchoalveolar lavage (BAL) fluid of patients with lung cancer (n = 32) and patients with chronic obstructive pulmonary disease (n = 22). BAL fluid was centrifuged to separate the supernatant from the cellular component. Cells were lysed in a detergent and cell-associated TfR was measured by enzyme-linked immunosorbent assay (ELISA) and expressed as ng 10(-6) cells in this cellular component. There was no difference in serum sTfR between the cancer and chronic obstructive pulmonary disease (COPD) groups. A higher level of cell-associated TfR was found in BAL of non-small-cell lung cancer patients than in COPD patients (P = 0.01). The calculated number of TfR molecules per cell in BAL correlated positively with the percentage of macrophages in BAL (P < 0.0001), suggesting that cell-associated TfR in BAL originates primarily from macrophages in this fluid. No correlation existed between BAL cell-associated TfR and tumour size, nodal status, the presence of metastases and serum sTfR. BAL cell-associated TfR was negatively correlated with BAL supernatant neuron-specific enolase (NSE) (P = 0.01). A combination of BAL supernatant NSE and cell-associated TfR detected lung cancer with a sensitivity of 91%, a specificity of 59% and positive and negative predictive values of 81% and 71% respectively. In conclusion, BAL cell-associated TfR may help in the differential diagnosis of lung cancer vs pneumonia

Aging into Perceptual Control: A Dynamic Causal Modeling for fMRI Study of Bistable Perception

Aging is accompanied by stereotyped changes in functional brain activations, for example a cortical shift in activity patterns from posterior to anterior regions is one hallmark revealed by functional magnetic resonance imaging (fMRI) of aging cognition. Whether these neuronal effects of aging could potentially contribute to an amelioration of or resistance to the cognitive symptoms associated with psychopathology remains to be explored. We used a visual illusion paradigm to address whether aging affects the cortical control of perceptual beliefs and biases. Our aim was to understand the effective connectivity associated with volitional control of ambiguous visual stimuli and to test whether greater top-down control of early visual networks emerged with advancing age. Using a bias training paradigm for ambiguous images we found that older participants (n = 16) resisted experimenter-induced visual bias compared to a younger cohort (n = 14) and that this resistance was associated with greater activity in prefrontal and temporal cortices. By applying Dynamic Causal Models for fMRI we uncovered a selective recruitment of top-down connections from the middle temporal to lingual gyrus by the older cohort during the perceptual switch decision following bias training. In contrast, our younger cohort did not exhibit any consistent connectivity effects but instead showed a loss of driving inputs to orbitofrontal sources following training. These findings suggest that perceptual beliefs are more readily controlled by top-down strategies in older adults and introduce age-dependent neural mechanisms that may be important for understanding aberrant belief states associated with psychopathology

Use of Dramatization to Teach Cardiac Cycle Physiology to Medical Students

Part of the educator’s mission is to develop new methodologies that promote active learning. This study examines the use of dramatization of the cardiac cycle in medical school. Two groups (n=42, 21 each) of first-year medical students participated. Group A was initially taught through dramatization alone, while Group B was taught through lecture followed by dramatization. Students completed a 13-item assessment (pretest and posttest) designed to measure knowledge of the cardiac system immediately before and after participating in the dramatization activity. Six months later students completed a third posttest assessment (follow-up) to assess their retention of cardiac cycle content. Students also rated their prior knowledge of general physiology and their confidence level in learning the material presented. Students in groups A and B scored at the same approximate level on the initial pretest (57% and 61% respectively, p=0.53). Scores for both groups increased significantly on the immediate posttest compared to pretest (p<0.0001). Both groups scored equally well on the immediate posttest (88% and 89% respectively, p=0.48), even though Group A had been taught the content based on dramatization alone. Both groups subsequently scored equally well on the six-month follow-up assessment (p<0.0001). Levels of self-reported confidence in knowledge also increased in both groups (p<0.05). This interactive teaching method increases student confidence in their knowledge and promotes learning in the short term equally well when compared to more traditional teaching methods. Implications for further research on dramatization as a teaching method are explored

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.

Purpose:To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods:In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results:A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3-4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57-100%. Conclusions:The combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration

Disaster risk assessment in health centers of Iran University of Medical Sciences in functional, non structural & structural components during 2015-2016

Background and aims: Disasters and events including natural and man-made disasters cause several harmful consequences in society. Health sector has an essential role in reducing deaths and injuries during disasters. Therefore, the present study was performed to study disaster safety and risk assessment in health facilities of Iran University of Medical Sciences in functional, non structural & structural components in 2015-2016. Methods: This study is cross-sectional. To conduct the study, we used Disaster Risk Assessment in Primary Health Care Facilities Guidelines and forms of recognition threatening risks, functional preparedness assessment tool, non-structural & structural vulnerability assessment tool in 214 health units covered by Iran University of Medical Sciences. After summing up the results of all centers, safety level, vulnerability and preparedness for centers were calculated as percentage. Results: Based on the results functional preparedness level in health centers for Iran University of Medical Sciences is 23, safety of non-structural, structural elements and total safety are 27, 20 and 22 , respectively. Also, safety level index in disaster 3 form 10 was estimated. Conclusion: According to the results current situation of disaster preparedness centers is far from the favorable level. This condition is caused by lack of coherent organization for disaster risk management, lack of sufficient funds and knowledge of this context. As a result, appropriate measures in disaster risk management, especially in increasing the understanding of disaster risk at the community and authorities level should be done. © 2018 Universiteit Gent. All rights reserved

A pilot study examining the prognostic utility of tumor shrinkage on cone-beam computed tomography (CBCT) for stage III locally advanced non-small cell lung cancer patients treated with definitive chemoradiation

There has been growing interest in utilizing information from cone-beam computed tomography (CBCT) to help guide both treatment delivery and prognosis. In this assessment of locally advanced unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation, we aimed to determine the survival advantage associated with using CBCT to measure tumor regression. Patient, tumor, and treatment characteristics were collected. The serial tumor shrinkage for each patient was determined from tumor volume contours on weekly CBCTs. Survival analysis was performed using the Kaplan-Meier technique and a Cox proportional hazards model. At least two-thirds of patients had a tumor volume reduction of at least 5% after each week of chemoradiation. A weekly reduction in tumor volume of 5% or greater seen on the CBCT images during radiation therapy was significantly associated with improved overall survival, which remained significant when adjusted for age, histology, grade, and T- and N-stages

Number of mortality, chronic obstructive pulmonary disease and acute myocardial infarction due to exposure to sulfur dioxide in Tehran, during 2005-2014

Introduction: Air pollution has adverse effects on human health and causes various health endpoints including mortality, cardiovascular and respiratory diseases. Therefore, the aim of this sstudy was to investigate number of total mortality, cardiovascular and respiratory mortality, acute myocardial infarction and chronic obstructive pulmonary disease due to exposure to sulfur dioxide in Tehran during 2005-2014 was performed. Materials and Methods: This is a descriptive-cross sectional study. At the beginning, hourly data during 2005-2014 were taken from Tehran environmental protection agency and Air Quality Control Company. Then, according to the WHO validated guidelines and statistical parameters, quantifying health effects were calculated in Excel. Finally, assessment of health effects with the software was performed. Results: Annual average concentrations for SO2 was 44, 86, 89, 112, 82, 81, 59, 51, 40 and 39 μg/m3 during 2005-2014, respectively. The number of total mortality caused by exposure to SO2 in the past decade was 8836, total number of cardiovascular and respiratory mortality in the past decade was 7335 and 1915, and total number of chronic obstructive pulmonary disease and acute myocardial infarction in the past decade was 1806 and 3478 people in 2005-2014 years. Conclusion: Air pollution, especially sulfur dioxide leads to mortality and morbidity in a lot of people. According to the results of this study actions, policies, planning and management to reduce air pollution preparedness of hospitals and health centers, educating the public should be accomplished. © 2017, Semnan University of Medical Sciences. All rights reserved

Comparison of serum and bronchoalveolar lavage fluid sialic acid levels between malignant and benign lung diseases

BACKGROUND: It is known that tissue and serum sialic acid levels may be altered by malignant transformation. In this study, sialic acid levels were determined in bronchoalveolar lavage fluid (BAL) and serum in two groups of patients with lung cancer and non-malignant diseases of the lung. METHODS: Colorimetric methods were used for determination sialic acid in serum and in BAL samples. Flexible bronchoscopy was used to obtain the latter. RESULTS: Sialic acid levels in bronchoalveolar lavage fluid and serum did not show any statistically significant difference between subjects with malignant and the non-malignant lung diseases (p > 0.05). Sialic acid levels were also unrelated to the stage and localization of the tumor (p > 0.05). CONCLUSIONS: Sialic acid levels do not appear to be a good marker for discriminating malignant from non-malignant diseases of the lung