Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro and in preclinical mouse model

Ovarian cancer is the leading cause of cancer related deaths in women. Genetic alterations including overexpression of EGFR play a crucial role in ovarian carcinogenesis. Here we evaluated the effect of phenethyl isothiocyanate (PEITC) in ovarian tumor cells in vitro and in vivo. Oral administration of 12 μmol PEITC resulted in drastically suppressing ovarian tumor growth in a preclinical mouse model. Our in vitro studies demonstrated that PEITC suppress the growth of SKOV-3, OVCAR-3 and TOV-21G human ovarian cancer cells by inducing apoptosis in a concentration-dependent manner. Growth inhibitory effects of PEITC were mediated by inhibition of EGFR and AKT, which are known to be overexpressed in ovarian tumors. PEITC treatment caused significant down regulation of constitutive protein levels as well as phosphorylation of EGFR at Tyr1068 in various ovarian cancer cells. In addition, PEITC treatment drastically reduced the phosphorylation of AKT which is downstream to EGFR and disrupted mTOR signaling. PEITC treatment also inhibited the kinase activity of AKT as observed by the down regulation of p-GSK in OVCAR-3 and TOV-21G cells. AKT overexpression or TGF treatment blocked PEITC induced apoptosis in ovarian cancer cells. These results suggest that PEITC targets EGFR/AKT pathway in our model. In conclusion, our study suggests that PEITC could be used alone or in combination with other therapeutic agents to treat ovarian cancer. © 2012 Loganathan et al

Cerebrospinal metastases in malignant childhood astrocytomas

Over a period of five years, antemortem diagnosis of leptomeningeal spread was made in six of thirteen children with high grade astrocytomas. These included four of seven children with hemispheral tumors and two of six children with malignant brainstem gliomas. Leptomeningeal spread was diagnosed by the clinical picture and CSF profile. Meningeal spread occurred an average of 5 months (range 0–16) after initial diagnosis of tumor was made. Several patients responded well to local radiation and/ or chemotherapy. Mean survival after evidence of meningeal spread was 7 months (range 2–16) with one patient still alive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45379/1/11060_2004_Article_BF00177897.pd

Нормативно-правові аспекти дослідження витрат торговельних підприємств

У статті досліджено міжнародні та національні нормативно-правові акти, що розкривають суть та методологічні аспекти формування витрат підприємств у бухгалтерському і податковому обліку. (In the article are investigated standard-legal sources that open methodological aspects of formation of costs of the enterprises in the accounting and tax account.

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears: one institution's experience

To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age >48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepthelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies

Diagnostic cytology and its histopathologic bases

Upon entering the study of cytopathology, one of the 'must-have' books is Dr. Koss's Diagnostic Cytology. It is one of the so-called bibles of cytopathology, which many of us have in our libraries and refer to often. First published in 1961, this book and its teachings are timeless. Diagnostic Cytology captures the art of cytopathology, history, daily clinical practice and potential diagnostic pitfalls, and future directions and applications. It reads like a direct mentoring session from one of our beloved fathers of cytopathology. Gazing through the fifth edition, one is immediately excited by the artistry and science of our craft and wishes to immediately purchase the book. This is certainly due to the extensive content and outstanding pictures in the text but also to the expertise and wisdom shared by Drs. Koss and Melamed and the other 18 chapter authors. This fifth edition is simply exquisite. It is extensively expanded, with each organ system having a dedicated chapter, and there is particular emphasis on avoiding diagnostic errors. It is a highly readable text, encompassing the breadth of exfoliative and aspiration cytology. The book is divided into 47 chapters within 3 major sections comprising general cytology, diagnostic cytology of organs and techniques in diagnostic cytology. The organization of the book follows a natural flow, beginning with the history and basic principles of cytology, comprehensive chapters on exfoliative and fine needle aspiration of every body site, and detailed descriptions of techniques, including preparations, staining and ancillary techniques. The first section is devoted to general diagnostic cytology, including its history and principles, cytogenetics, cell recognition and classification, morphology of cell injury, and concepts of molecular biology and neoplasia. These chapters are well organized, detailed and lucid. The second section encompasses diagnostic cytology of all organs, beginning with the female reproductive tract. The full spectrum of gynecologic cytology is rigorously detailed and illustrated. Given all the recent changes in the area of cervical cancer screening, utilization of liquid-based cytology and human papillomavirus testing, these expanded chapters accomplish the difficult task of being meticulous and thoroughly up to date while providing an outstanding historical perspective. Dr. Koss does not shy away from expressing his feelings and stating the truth-for example, 'At all times, the pattern of abnormalities is more significant than the abnormalities of the individual cell.' His opinions on the liquid-based preparations are thought provoking and worthy of serious discussion. Particular emphasis on diagnostic difficulties and potential errors, with superb illustrations and photomicrographs and a clear text, make these chapters indispensable. The cytology of each organ site is systematically covered in individual chapters, providing in-depth discussions, reviews of the literature, and pertinent diagnostic points and challenges. When applicable, ancillary techniques, including immunocytochemistry, flow cytometry and molecular analysis, are described thoroughly. Each organ chapter is beautifully illustrated, comprehensive and outstanding. It is a tribute to the authors that in a tome of this size, references are current and up to date; a few from the year 2004 make the list. Meticulous preparatory, fixation and staining techniques are described in the last section and serve as an excellent reference. In addition, immunochemistry, digital analysis and flow cytometry each have dedicated chapters. This book contains more than 3,000 full-color photos of outstanding quality and also includes an image bank DVD. There are numerous easy-to-read diagrams, schematics, tables and lists highlighting cytomorphologic features and diagnostic dilemmas. Boldface text emphasizes key points throughout the book. Diagnostic Cytology superbly accomplishes its task of being an in-depth text that covers the broad field of human cytopathology. In the fifth edition, Dr. Koss continues to share his teachings, experience and wisdom-qualities unique to this book among the many available now. The particular emphasis on avoiding diagnostic errors further challenges all of us to become better diagnosticians. When Dr. Koss speaks about cytopathology, he exudes passion and scholarship; this book is no different. This is not a book about cytopathology; it is cytopathology! It is an extremely informative and practical text that continues to be required reading. We highly recommend it for practicing cytopathologists, pathology residents and fellows, and cytotechnologist

Entamoeba gingivalis pulmonary abscess - Diagnosed by fine needle aspiration

Entamoeba gingivalis (E. gingivalis ) is a parasitic protozoa of the oral cavity, most often found in gingival tissues around the teeth associated with poor oral hygiene. Here, we report a case of E. gingivalis in a pulmonary CT guided fine needle aspiration material, from a 60-year-old man with newly found lung mass. On site Diff-Quik® smear examination revealed the presence of marked acute inflammation, colonies of actinomyces, and a number of ‘large macrophages-like organisms’. Upon examination of the additional material, organisms morphologically consistent with E. gingivalis were identified. Pulmonary mass resolved after six weeks of treatment with antibiotics (Clindamycin followed by Penicillin). Proper recognition and distinction between E. gingivalis and other species of Entamoeba is important for the management of patients