Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma

SummaryTumor heterogeneity has been implicated in tumor growth and progression as well as resistance to therapy. We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell. The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies

Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine

Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. We developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management

مقایسه تطبیقی استیضاح مقام رییس‌جمهوری در ایران و ایالات متحده آمریکا از منظر عناصر متشکله مفهوم حاکمیت قانون

Background and Aim: The presidency, as the highest executive authority in the country, has the most administrative and executive powers. As much as the dimensions of authority increase, the risks of corruption and abuse of power also increase. The aim of the present study is to investigate the mechanism of impeachment as a tool to control corruption by considering the elements of the rule of law. Materials and Methods: This research is theoretical in sort of type and the method is descriptive-analytical. The method of data collection is library and has been done by referring to documents, books and articles. Ethical Considerations: In order to organize this research, while regarding the authenticity of the texts, honesty and fidelity have been observed. Findings: Political variables have a flexible and fluid framework that everyone can offer a different interpretation according to their own taste. This feature challenges the exercise of the rule of law, and in particular accuracy and transparency in the process of impeachment. For this reason, certain criteria should be provided for identifying political variables such as inadequacy for management. Conclusion: Considering the presidential system as a system in which the president himself has more power than the president in the semi-presidential system, the impeachment of the president in the presidential system should require a lot of research and many processes by the parliament. However, in the semi-presidential system of the Islamic Republic, due to the division of power between the president and the Supreme Leader, the impeachment of the president is possible, along with the statements of the parliamentarians and their vote.   Please cite this article as: Feghahati GH, Masoud GH-H, Raei M, Akhavanfard M. A Comparative Study of the Impeachment of the President in Iran and the United States of America from the Perspective of Constituent Elements of the Concept of the Rule of Law. Bioethics Journal, Special Issue on Ethical & Legal Reflections 2021; 283-297.زمینه و هدف: مقام ریاست جمهوری به عنوان عالی‌ترین مقام اجرایی در کشور، از نظر اداری و اجرایی بیشترین حدود اختیارات را دارا می‌باشد. به هر میزان که حدود اختیارات افزایش یابد، خطرات ناشی از فساد و سوءاستفاده از قدرت نیز افزایش می‌یابد. در پژوهش حاضر هدف این است که سازوکار استیضاح به عنوان یک ابزار کنترل و مهار فساد با در نظرگرفتن عناصر حکومت قانون مورد بررسی قرار گیرد. مواد و روش‌ها: این تحقیق از حیث نوع، نظری است و ‌روش آن به صورت توصیفی ـ تحلیلی می‌باشد. جمع‏آوری اطلاعات نیز به شیوه کتابخانه‏ای و با مراجعه به اسناد، کتب و مقالات، صورت گرفته است. ملاحظات اخلاقی: در تمام مراحل نگارش پژوهش حاضر، ضمن پایبندی به اصالت متون، صداقت و امانتداری رعایت شده است. یافته‌ها: متغیرهای سیاسی دارای چارچوبی منعطف و سیال می‌باشند که هر کس می‌تواند بنا به سلیقه خود، تفسیر و قرائتی متفاوت از آن ارائه دهد. این ویژگی باعث می‌شود که اعمال حاکمیت قانون و به طور خاص جزمیت و شفافیت در فرایند استیضاح با چالش مواجه شود. به همین دلیل باید معیارهای مشخصی برای تشخیص متغیرهای سیاسی مانند عدم کفایت برای مدیریت، پیش‌بینی شود. نتیجه‌گیری: با در نظرگرفتن نظام ریاستی به عنوان نظامی که شخص رییس‌جمهور در آن قدرتی فراتر از قدرت رییس‌جمهور در نظام نیمه‌ریاستی دارد، باید استیضاح رییس‌جمهور در نظام ریاستی نیازمند تحقیقات فراوان و گذراندن فرایندهای بسیاری از جانب پارلمان باشد، اما در نظام نیمه‌ریاستی مدل جمهوری اسلامی به دلیل تقسیم قدرت میان رییس‌جمهور و مقام رهبری، استیضاح رییس‌جمهور ضمن بیانات نمایندگان و رأی آن‌ها مبنی بر این امر، میسر است