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Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Development of phenotypic indexes for the description of morphological injury in breast cancer cell mitochondria.
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Sub-category:
Tumor/Cell Biology
Category:
Tumor Biology
Meeting:
2009 ASCO Annual Meeting
Session Type and Session Title:
This abstract will not be presented at the 2009 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract No:
e22055
Citation:
J Clin Oncol 27, 2009 (suppl; abstr e22055)
Author(s):
L. Putignani, S. Raffa, R. Pescosolido, F. Signore, D. Menichella, R. Boldrini, M. Torrisi, P. Grammatico; Bambino Gesù, Rome, Italy; S. Andrea Hospital, Rome, Italy; S. Camillo-Forlanini Hospital, Rome, Italy; Bambino Gesù Hospital, Rome, Italy; S. Andrea Hospital, University Sapienza, Rome, Italy
Abstract Disclosures
Faculty and Discussant Disclosures
Annual Meeting Planning Committee Disclosures
2009 Annual Meeting Proceedings Part I Errata
Abstract:
Background: Mitochondriopathy has been recently rekindled as new cancer theory. We report on structural damage of breast-infiltrating ductal carcinoma (IDC) mitochondria characterised by reduced expression levels of the oxidative phosphorylation system (OXPHOS). Methods: Mitochondria from HMC-1 (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures, traced by Mitotracker, were assayed for OXPHOS expression levels using cryo-immunoelectron microscopy (CIEM) quantitative labelling and fluorescence immunolabelling on unfractionated HMC-1 and HEMC cells. Convolution degeneration was established by transmission electron microscopy (TEM). Twenty different cell sections for both HMC-1 and HEMC cells, including 65 and 72 mitochondria, respectively, were randomly recorded and quantitatively analyzed for the percentage of area occupied by intact cristae to provide a grading of mitochondrial damage (cristae loss index). Results: Depressed expression levels were detected for all HMC-1 OXPHOS complexes by CIEM. Normalized labelling density (HEMC/HMC-1), expressed as colloidal gold particles/mitochondrial area (ρ) provided the following values: 1.77 for the NADH-ubiquinone oxidoreductase complex I NDUFS3; 1.86 for the succinate- dehydrogenase complex II SDH-B protein; 1.63 for the ubiquinol cytochrome c reductase complex III UQCRC2; 4.88 and 1.58 for the cytochrome-oxidase complex IV (CO) subunit I and IV, respectively; 2.70 for the ATP-synthase complex V F1β protein. Fluorescence immunolabelling confirmed CIEM quantitative data. MitoTracker's co-staining showed altered membrane potential and permeability. Injury grading was categorised assigning three levels of morphological damage: i) severe, ii) moderate, iii) slight, corresponding to 0 % (6.2 % and 1.4 % for HMC-1 and HMEC, respectively), 1-50 % (21.5 % and 2.8 % for HMC-1 and HMEC, respectively) and 51-75 % (44.6 % and 15.3 % for HMC-1 and HMEC, respectively) of area occupied by intact cristae (p<0.0001, χ2 Test). The entire HMC-1 mitochondrial damage resulted 3.7 times higher than that observed for HMEC cells (72.3HMC-1 %/19.5HMEC %). Conclusions: New phenotypic harm indexes for IDC cell mitochondria might provide new hallmarks in breast cancer cell biology
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Nodular renal blastoma in kidney with multicystic dysplasia. Report of a case.
No full textThe clinico-pathologic association of nodular renal blastema, multicystic kidney and obstructive uropathy has been recently identified. We report on a female patient diagnosed as having unilater multicystic dysplasia by prenatal ultrasonography. The patient was nephrectomized at the age of 6 1/2 months. Examination of the resected kidney revealed multiple unilocular cysts in the cortex and hypoplasia of the homolateral ureter; histological study confirmed the presence of multiple cysts limited to the renal cortex, and revealed, among them, multiple cortical metanephric blastema cells islands. Our case supports a relationship between nodular renal blastema, cortical cysts and obstructive uropathy; ureter hypoplasia could cause intraluminal back pressure, with consequent abnormal development of the ampullae, normally endowed in nephronic anlagens induction, cystic tubular ectasia and persistence of nodular renal blastema. The peripheral location of renal nodular blastema and cysts supports a late error in nephrogenesis, at the time of formation of the last generation of nephrons
Evidence for a hybrid macrophage phenotype in erythrophagocytic histiocytosis
No full textPURPOSE: The phenotype of the proliferating cells in two patients with erythrophagocytic histiocytosis is described. These 6- and 18-month-old female patients presented with fever, anemia, hepatosplenomegaly, and lymphadenopathy. MATERIALS AND METHODS: Clinical histories were reviewed, and pathological specimens of both patients were studied by histology, and electron microscopy/immunohistochemistry using antibodies against macrophage and Langerhans cell (LC) antigens. RESULTS: Histology revealed prominent erythrophagocytosis of proliferating histiocytes. By immunohistochemistry, conventional macrophage (HAM-56, alpha 1-antitrypsin, alpha 1-antichymotrypsin, lisozyme, CD68, and alpha-subunit of S-100 protein) and LC (CD1a and S-100 protein) markers were positive, as well as double labeling for CD1a and alpha 1-antichymotrypsin, in a majority of proliferating cells. Ultrastructural examination revealed Birbeck granules and prominent phagolysosomes frequently in the same cell. CONCLUSIONS: The hybrid ultrastructural and immunohistochemical phenotype between phagocytic macrophage and LC of proliferating histiocytes supports the common origin of these different histiocyte subtypes. This unusual phenotype might be the expression of the proliferating (hybrid) precursor or be the effect of unknown stimuli. Additional cases of childhood erythrophagocytic histiocytosis should be studied with immunophenotyping and ultrastructure to determine whether the hybrid phenotype represents a specific entity or an epiphenomenon
THE MIDDLE PLEISTOCENE FOSSILIFEROUS SEQUENCE OF GROTTA DEI FIORI (SARDINIA, ITALY): MULTIDISCIPLINARY ANALYSIS
No full textABSTRACT - A multidisciplinary methodological approach (palaeontological, sedimentological and stable isotope analyses) was performed to analyse the fossiliferous sequence exposed in the “Grotta dei Fiori” cave (South Western Sardinia, Italy), where several small mammal remains (Microtus (Tyrrhenicola) henseli, Rhagamys orthodon, “Nesiotites” similis and Prolagus sardus) were discovered together with scanty remains of the endemic canid Cynotherium, and birds. Morphology and morphometry of first lower molars (M1) of Microtus (Tyrrhenicola)henseli from Grotta dei Fiori show that primitive and advanced morphotypes are present in each fossiliferous level. The relative frequency of morphotypes indicates that the population from “Grotta dei Fiori” might be regarded as more advanced than Microtus (Tyrrhenicola) sondaari from Xg3 fissure of Monte Tuttavista (Eastern Sardinia, late Early Pleistocene) and more primitive than the most of ?Middle and Late Pleistocene populations of Microtus (Tyrrhenicola) henseli from Sardinia. All in all, the data thus far provided by sedimentology and geochemistry indicate that the fossiliferous sequence of “Grotta dei Fiori” was deposited under climatic conditions characterized by an alternation of wet and dry periods. Taking into account the evolutionary degree of voles, 13C/12C and 16O/18O ratio and micromorphology of sediments, the hypothesis that the “Grotta dei Fiori” succession would be not older than the marine isotope stage (MIS) 11 cannot be ruled out. The results obtained stress once more the difficulty of a precise chronologic setting for deposits filling caves when no absolute date is available, and highlight the usefulness of a multidisciplinary approach to define environmental context and, perhaps, constrain chronology
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