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Taylor P.A.,Core Oncology | Kry S.F.,Core Oncology | Followill D.S.,Core Oncology
International Journal of Radiation Oncology Biology Physics | Year: 2017

Purpose: To compare analytic and Monte Carlo-based algorithms for proton dose calculations in the lung, benchmarked against anthropomorphic lung phantom measurements. Methods and Materials: A heterogeneous anthropomorphic moving lung phantom has been irradiated at numerous proton therapy centers. At 5 centers the treatment plan could be calculated with both an analytic and Monte Carlo algorithm. The doses calculated in the treatment plans were compared with the doses delivered to the phantoms, which were measured using thermoluminescent dosimeters and film. Point doses were compared, as were planar doses using a gamma analysis. Results: The analytic algorithms overestimated the dose to the center of the target by an average of 7.2%, whereas the Monte Carlo algorithms were within 1.6% of the physical measurements on average. In some regions of the target volume, the analytic algorithm calculations differed from the measurement by up to 31% in the internal gross target volume (iGTV) (46% in the planning target volume), over-predicting the dose. All comparisons showed a region of at least 15% dose discrepancy within the iGTV between the analytic calculation and the measured dose. The Monte Carlo algorithm recalculations showed dramatically improved agreement with the measured doses, showing mean agreement within 4% for all cases and a maximum difference of 12% within the iGTV. Conclusions: Analytic algorithms often do a poor job predicting proton dose in lung tumors, over-predicting the dose to the target by up to 46%, and should not be used unless extensive validation counters the consistent results of the present study. Monte Carlo algorithms showed dramatically improved agreement with physical measurements and should be implemented to better reflect actual delivered dose distributions. © 2017 Elsevier Inc.

Sevenich L.,Albert Ludwigs University of Freiburg | Werner F.,Albert Ludwigs University of Freiburg | Gajda M.,Friedrich - Schiller University of Jena | Schurigt U.,Albert Ludwigs University of Freiburg | And 5 more authors.
Oncogene | Year: 2011

Elevated expression of the cysteine protease cathepsin B (CTSB) has been correlated with a poor prognosis for cancer patients. In order to model high CTSB expression in mammary cancer, transgenic mice expressing human CTSB were crossed with transgenic polyoma virus middle T oncogene breast cancer mice (mouse mammary tumor virus-PymT), resulting in a 20-fold increase in cathepsin B activity in the tumors of double-transgenic animals. CTSB expression did not affect tumor onset, but CTSB transgenic mice showed accelerated tumor growth with significant increase in weight for end-stage tumors, as well as an overall worsening in their histopathological grades. Notably, the lung metastases in the CTSB transgenic animals were found to be both significantly larger and to occur at a significantly higher frequency. Ex vivo analysis of primary PymT tumor cells revealed no significant effects from elevated CTSB levels on tumor cell characteristics, that is, the formation of tumor cell colonies and the sprouting of invasive strands from PymT cell spheroids. However, tumors from CTSB-overexpressing mice showed increased numbers of tumor-associated B cells and mast cells. In addition, more CD31 endothelial cells were detected in these tumors, correlating with higher levels of vascular endothelial growth factor (VEGF) being present in the tumor and serum. We conclude that elevated proteolytic CTSB activity facilitates progression and metastasis of PymT-induced mammary carcinomas, and is associated with increased immune cell infiltration, enhanced VEGF levels and the promotion of tumor angiogenesis. © 2011 Macmillan Publishers Limited All rights reserved.

Papeo G.,Nerviano Medical science Srl | Pulici M.,Core Oncology
Molecules | Year: 2013

From the second half of the 19th century up to modern times, the tremendous contribution of Italian chemists to the development of science resulted in the discovery of a number of innovative chemical transformations. These reactions were subsequently christened according to their inventors' name and so entered into the organic chemistry portfolio of "named organic reactions". As these discoveries were being conceived, massive social, political and geographical changes in these chemists' homeland were also occurring. In this review, a brief survey of known (and some lesser known) named organic reactions discovered by Italian chemists, along with their historical contextualization, is presented. © 2013 by the authors;.

Piutti C.,Nerviano Medical science srl | Quartieri F.,Core Oncology
Molecules | Year: 2013

Nearly forty years ago, at the University of Rome, Giovanni Piancatelli and co-workers discovered the acid-catalyzed water-mediated rearrangement of 2-furylcarbinols into 4-hydroxycyclopentenones. These motifs are core components of several pharmacologically active compounds and precursors of many natural products. The main features of this reaction are the simple experimental conditions, the stereochemical outcome and the generality of the procedure. Consequently, a re-emergence of this reaction has been seen recently, including developments of the Piancatelli rearrangement with some interesting inter- and intramolecular variants. This review will mainly focus on the general aspects of the reaction along with its more recent applications. © 1996-2013 MDPI AG.

Bortolomai I.,Unit of Molecular Therapies | Canevari S.,Unit of Molecular Therapies | Facetti I.,Unit of Molecular Therapies | De Cecco L.,Core Oncology | And 5 more authors.
Cell Cycle | Year: 2010

To investigate the tumor fraction with cancer stem/tumor initiating cell (CSC/TIC) characteristics, we tested the human cervical carcinoma cell lines A431, Caski and SiHa, by growth as non-adherent spheres in specific media and aldehyde dehydrogenase (ALDH) enzymatic activity. A good correlation between the two parameters was observed and the highest levels were observed in A431 cell line that was selected for characterization of the CSC/TIC fraction. A431 parental cells already displayed characteristics common to CSC/TIC, such as sphere forming efficiency, adherent holoclone formation and high ALDH activity. Non-adherent spheres maintained or increased these properties, and, in particular, ALDH-positive fraction increased from 46 to 65% and a transient induction of stem cell markers such as Nanog, Nestin and Oct4 was observed. Furthermore, a significant increase of paraclone forming cells was observed, suggesting that differentiation took place inside sphere cell populations. As compared to parental cells, spheres were characterized by: (1) a ten-fold higher verapamil-sensitive side population fraction; (2) the appearance of a podoplanin-positive subpopulation characterized by a small cell size; (3) the ability to propagate tumors in nude mice at a lower cell dose. The global gene expression analysis demonstrated a strong and reversible modulation of 'sphere' phenotype in comparison to parental and sphere cells re-induced to adherent conditions. All together our results indicated that the growth of A431 cells as a non-adherent sphere was not sufficient by itself to define a stem-like population, but it was essential for the emergence of a small population of tumor cells with CSC properties. © 2010 Landes Bioscience.

Caccia D.,Fondazione IRCCS Instituto Nazionale Dei Tumori | Dugo M.,Core Oncology | Callari M.,Core Oncology | Callari M.,Fondazione IRCCS Instituto Nazionale Dei Tumori | Bongarzone I.,Fondazione IRCCS Instituto Nazionale Dei Tumori
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2013

Over recent years, analyses of secretomes (complete sets of secreted proteins) have been reported in various organisms, cell types, and pathologies and such studies are quickly gaining popularity. Fungi secrete enzymes can break down potential food sources; plant secreted proteins are primarily parts of the cell wall proteome; and human secreted proteins are involved in cellular immunity and communication, and provide useful information for the discovery of novel biomarkers, such as for cancer diagnosis. Continuous development of methodologies supports the wide identification and quantification of secreted proteins in a given cellular state. The role of secreted factors is also investigated in the context of the regulation of major signaling events, and connectivity maps are built to describe the differential expression and dynamic changes of secretomes. Bioinformatics has become the bridge between secretome data and computational tasks for managing, mining, and retrieving information. Predictions can be made based on this information, contributing to the elucidation of a given organism's physiological state and the determination of the specific malfunction in disease states. Here we provide an overview of the available bioinformatics databases and software that are used to analyze the biological meaning of secretome data, including descriptions of the main functions and limitations of these tools. The important challenges of data analysis are mainly related to the integration of biological information from dissimilar sources. Improvements in databases and developments in software will likely substantially contribute to the usefulness and reliability of secretome studies. This article is part of a Special Issue entitled: An Updated Secretome. © 2013 Elsevier B.V.

Jiang K.,Core Oncology
Applied Immunohistochemistry and Molecular Morphology | Year: 2016

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive carcinoma, with most patients diagnosed at an advanced stage, with a 5-year survival rate of around 5%. An urgent need exists for identifying better diagnostic, prognostic, and therapeutic markers for this lethal disease. Recently, CA125 has been identified in PDAC, and the aim of this research is to study the changes in CA125 expression during the progression of benign pancreatic tissue (BPT) to PDAC and to assess its value as a biomarker of tumor growth. To address these questions, the cellular levels of CA125 in BPT and PDAC were measured using immunohistochemistry and compared on the basis of tumor staging, and the tissue microarray technology were constructed using resected pancreatic tissues. The staining reactions for each case were evaluated semiquantitatively using the histologic score system. Our investigation demonstrates a consistent and significant upregulation of CA125 during the transition from BPT to PDAC. We also found a direct correlation between CA125 immunohistochemistry score and tumor stage (P=0.02). In conclusion, our data indicate that CA125 plays a direct role in pancreatic carcinogenesis and suggests that it may eventually be used as a diagnostic and/or prognostic biomarker of pancreatic cancer. Prospective studies are recommended to evaluate further the diagnostic and prognostic capabilities of CA125 in PDAC, and further studies are warranted to assess the use of CA125 as a therapeutic marker. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

Yang T.X.,St George Hospital | Morris D.L.,St George Hospital | Morris D.L.,University of New South Wales | Chua T.C.,St George Hospital | And 2 more authors.
Diseases of the Colon and Rectum | Year: 2013

BACKGROUND: Pelvic exenteration is a potentially curative treatment for locally advanced primary or recurrent rectal cancer. OBJECTIVE: This systematic review examines the current evidence regarding clinical and oncological outcomes in patients with locally advanced primary and recurrent rectal cancer who undergo pelvic exenteration. DATA SOURCES: A literature search of PubMed, Medline, and the Cochrane library was undertaken, and studies published in the English language from January 2000 to August 2012 were identified. STUDY SELECTION: Prospective and retrospective studies that report outcomes of pelvic exenteration for primary advanced and locally recurrent rectal cancer with or without subgroup evaluation were included for examination. MAIN OUTCOME MEASURES: Oncological outcomes included 5-year survival, median survival, and local recurrence rates. Clinical outcomes included complication rates and perioperative mortality rates. RESULTS: A total of 23 studies with 1049 patients were reviewed. The complication rates ranged from 37% to 100% (median, 57%) and the perioperative mortality rate ranged from 0% to 25% (median, 2.2%). The rate of local recurrence ranged from 4.8% to 61% (median, 22%). The median survival for primary advanced rectal cancers was 14 to 93 months (median, 35.5 months) and 8 to 38 months (median, 24 months) for locally recurrent rectal cancer. LIMITATIONS: Our review was limited by the small sample sizes from single-institutional studies reporting outcomes over long periods of time with heterogeneity in both the disease and treatments reported. CONCLUSIONS: Although the human costs and risks are significant, the potentially favorable survival outcomes make this acceptable in the absence of other effective treatment modalities that would otherwise result in debilitating symptoms that afflict patients who have advanced pelvic malignancy. © The ASCRS 2013.

Core Oncology | Date: 2012-11-13

Localizing and stabilizing template and armature for breast microseed treatment.

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