Nuovi protocolli chemioterapici per i sarcomi dei tessuti molli ad alto grado di malignita' negli adulti: Risultati clinici, radiologici e istologici comparando chemioterapia standard e orientata sull'isotopo

I sarcomi dei tessuti molli sono un gruppo eterogeneo di tumori maligni di origine mesenchimale che si sviluppa nel tessuto connettivo. Il controllo locale mediante escissione chirurgica con margini ampi associato alla radioterapia e chemioterapia è il trattamento di scelta. Negli ultimi anni le nuove scoperte in campo biologico e clinico hanno sottolineato che i diversi istotipi posso essere considerati come entità distinte con differente sensibilità alla chemioterapia pertanto questa deve essere somministrata come trattamento specifico basato sull’istologia. Tra Ottobre 2011 e Settembre 2014 sono stati inclusi nel protocollo di studio 49 pazienti con sarcomi dei tessuti molli di età media alla diagnosi 48 anni (range: 20 - 68 anni). I tumori primitivi più frequenti sono: liposarcoma mixoide, sarcoma pleomorfo indifferenziato, sarcoma sinoviale. Le sedi di insorgenza del tumore erano più frequentemente la coscia, il braccio e la gamba. 35 pazienti sono stati arruolati nel Braccio A e trattati con chemioterapia standard con epirubicina+ifosfamide, 14 sono stati arruolati nel Braccio B e trattati con chemioterapia basata sull’istotipo. I dati emersi da questo studio suggeriscono che le recidive locali sembrano essere correlate favorevolmente alla radioterapia ed ai margini chirurgici adeguati mentre la chemioterapia non sembra avere un ruolo sul controllo locale della malattia. Anche se l'uso di terapie mirate, che hanno profili di tossicità più favorevoli e sono quindi meglio tollerate rispetto ai farmaci citotossici è promettente, tali farmaci hanno prodotto finora risultati limitati. Apparentemente l’insieme delle terapie mirate non sembra funzionare meglio delle terapie standard, tuttavia esse devono essere esaminate per singolo istotipo e confrontate con il braccio di controllo. Sono necessari studi randomizzati controllati su ampie casistiche per valutare l’efficacia delle terapie mirate sui differenti istotipi di sarcomi dei tessuti molli. Inoltre, nuovi farmaci, nuove combinazioni e nuovi schemi posologici dovranno essere esaminati per ottimizzare la terapia.

Systematics, phylogeny and biogeography of Juncaginaceae

I investigated the systematics, phylogeny and biogeographical history of Juncaginaceae, a small family of the early-diverging monocot order Alismatales which comprises about 30 species of annual and perennial herbs. A wide range of methods from classical taxonomy to molecular systematic and biogeographic approaches was used. rnrnIn Chapter 1, a phylogenetic analysis of the family and members of Alismatales was conducted to clarify the circumscription of Juncaginaceae and intrafamilial relationships. For the first time, all accepted genera and those associated with the family in the past were analysed together. Phylogenetic analysis of three molecular markers (rbcL, matK, and atpA) showed that Juncaginaceae are not monophyletic. As a consequence the family is re-circumscribed to exclude Maundia which is pro-posed to belong to a separate family Maundiaceae, reducing Juncaginaceae to include Tetroncium, Cycnogeton and Triglochin. Tetroncium is weakly supported as sister to the rest of the family. The reinstated Cycnogeton (formerly included in Triglochin) is highly supported as sister to Triglochin s.str. Lilaea is nested within Triglochin s. str. and highly supported as sister to the T. bulbosa complex. The results of the molecular analysis are discussed in combination with morphological characters, a key to the genera of the family is given, and several new combinations are made.rnrnIn Chapter 2, phylogenetic relationships in Triglochin were investigated. A species-level phylogeny was constructed based on molecular data obtained from nuclear (ITS, internal transcribed spacer) and chloroplast sequence data (psbA-trnH, matK). Based on the phylogeny of the group, divergence times were estimated and ancestral distribution areas reconstructed. The monophyly of Triglochin is confirmed and relationships between the major lineages of the genus were resolved. A clade comprising the Mediterranean/African T. bulbosa complex and the American T. scilloides (= Lilaea s.) is sister to the rest of the genus which contains two main clades. In the first, the widespread T. striata is sister to a clade comprising annual Triglochin species from Australia. The second clade comprises T. palustris as sister to the T. maritima complex, of which the latter is further divided into a Eurasian and an American subclade. Diversification in Triglochin began in the Miocene or Oligocene, and most disjunctions in Triglochin were dated to the Miocene. Taxonomic diversity in some clades is strongly linked to habitat shifts and can not be observed in old but ecologically invariable lineages such as the non-monophyletic T. maritima.rnrnChapter 3 is a collaborative revision of the Triglochin bulbosa complex, a monophyletic group from the Mediterranean region and Africa. One new species, Triglochin buchenaui, and two new subspecies, T. bulbosa subsp. calcicola and subsp. quarcicola, from South Africa were described. Furthermore, two taxa were elevated to species rank and two reinstated. Altogether, seven species and four subspecies are recognised. An identification key, detailed descriptions and accounts of the ecology and distribution of the taxa are provided. An IUCN conservation status is proposed for each taxon.rnrnChapter 4 deals with the monotypic Tetroncium from southern South America. Tetroncium magellanicum is the only dioecious species in the family. The taxonomic history of the species is described, type material is traced, and a lectotype for the name is designated. Based on an extensive study of herbarium specimens and literature, a detailed description of the species and notes on its ecology and conservation status are provided. A detailed map showing the known distribution area of T. magellanicum is presented. rnrnIn Chapter 5, the flower structure of the rare Australian endemic Maundia triglochinoides (Maundiaceae, see Chapter 1) was studied in a collaborative project. As the morphology of Maundia is poorly known and some characters were described differently in the literature, inflorescences, flowers and fruits were studied using serial mictrotome sections and scanning electron microscopy. The phylogenetic placement, affinities to other taxa, and the evolution of certain characters are discussed. As Maundia exhibits a mosaic of characters of other families of tepaloid core Alismatales, its segregation as a separate family seems plausible.

Management of infusion reactions in clinical trials and beyond: the US and EU perspectives

Monoclonal antibodies have expanded our cancer-fighting armamentarium in both the United States and Europe. While in general, monoclonal antibodies are well tolerated and do not have significant overlapping side effects with traditional cytotoxic agents, severe infusion reactions (IRs)--sometimes severe enough to be life threatening--have been reported. The pathophysiology of severe infusion reactions associated with monoclonal antibodies is poorly understood, but mechanisms are beginning to be elucidated. Geographic differences in the incidence of IRs have become apparent. Understanding the risk, recognizing the signs and symptoms, and being ready to promptly manage severe IRs are key for the clinician to avoid unnecessarily discontinuing these effective anticancer agents and prevent potentially tragic consequences for their patients. To date, clinical trials have incorporated monoclonal antibodies into combinations with standard cytotoxic regimens; it is expected that in time clinical trials will be testing promising new combinations utilizing multiple targeted agents, resulting in improved toxicity profiles and efficacy for cancer patients.

Behavioural isolation may facilitate homoploid hybrid speciation in cichlid fish

Hybrid speciation is constrained by the homogenizing effects of gene flow from the parental species. In the absence of post-mating isolation due to structural changes in the genome, or temporal or spatial premating isolation, another form of reproductive isolation would be needed for homoploid hybrid speciation to occur. Here, we investigate the potential of behavioural mate choice to generate assortative mating among hybrids and parental species. We made three-first-generation hybrid crosses between different species of African cichlid fish. In three-way mate-choice experiments, we allowed hybrid and nonhybrid females to mate with either hybrid or nonhybrid males. We found that hybrids generally mated nonrandomly and that hybridization can lead to the expression of new combinations of traits and preferences that behaviourally isolate hybrids from both parental species. Specifically, we find that the phenotypic distinctiveness of hybrids predicts the symmetry and extent of their reproductive isolation. Our data suggest that behavioural mate choice among hybrids may facilitate the establishment of isolated hybrid populations, even in proximity to one or both parental species.

Strange Relations. Cultural Translation of Noh Theatre in Ezra Pound’s Dance Poems and W. B. Yeats’s At the Hawk’s Well

Drawing on the reception of Noh drama by Ezra Pound and William Butler Yeats, the article analyses both the literary and cultural ‘translations’ of this form of Japanese theatre in their works, focusing on Yeats’s play At the Hawk’s Well (1917). I conceptualize ‘cultural translation’ as the staging of relations that mark a residual cultural difference. Referred to as ‘foreignizing’ in translation theory, this method enables what Erika Fischer-Lichte has termed a ‘liminal experience’ for the audience –– an effect Yeats intended for the performance of his play. It evokes situations in which opposites collapse and new ways of acting or new combinations of symbols can be tried out. Yeats’s play will be used to sketch how an analysis of relations could serve as a general model for the study of cultural transfer as cultural translation in general. Keywords: cultural translation, translation theory, performance, William Butler Yeats, Itō Michio, Ezra Pound, At the Hawk’s Well

Plio-Pleistocene diatom biostratigraphy from ODP Leg 177, Atlantic sector of the Southern Ocean

Seven sites were drilled during Ocean Drilling Program Leg 177 in the Atlantic sector of the Southern Ocean (SO) on a transect over the Antarctic Circumpolar Current from the Subantarctic to the Antarctic Zone. At four sites sediments were recovered with a Pliocene/Pleistocene sediment package of up to 580 m allowing the refinement of previous diatom zonation concepts. Samples were analyzed on stratigraphic distribution and abundance of diatom species. A refined diatom biozonation tied to the geomagnetic polarity record is proposed. For the middle and late Pleistocene two zonations applicable to the northern and southern area of the SO were constructed, considering different latitudinal distributions of biostratigraphic diatom marker species. The southern zonation for the Pleistocene relies on the occurrence of species of the genus Rouxia, R. leventerae and R. constricta n. sp. as well as on a revised last occurrence datum (LOD) of Actinocyclus ingens (0.38 Ma, late marine isotope stage (MIS) 11). The use of these new stratigraphic marker species refines the temporal resolution for biostratigraphic age assignment to up to 0.1 Myr. In particular the LOD of R. leventerae as an indicator for the MIS 6/5 boundary (Termination II) will improve future dating of carbonate-free Antarctic sediments. These new data were obtained from sediments of Sites 1093 and 1094 (Antarctic Zone). The northern zonation for the middle and late Pleistocene time interval is based on the Pleistocene abundance pattern of Hemidiscus karstenii which was already proposed by previous investigations (e.g. Gersonde and Barcena, 1998). One new species (R. constricta) and two new combinations (Fragilariopsis clementia, Fragilariopsis reinholdii) are proposed in this study.

Late Cenozoic silicoflagellate biostratigraphy, relative paleotemperature, and distribution of various genera and morphologic subgroups with remarks on noteworthy occurrences at DSDP Leg 86 Holes

A quantitative study of late Cenozoic silicoflagellates from the northwestern Pacific sites of Deep Sea Drilling Project Leg 86 shows a relative paleotemperature (Ts) gradient with lowest values (Ts = 30) in the north. Some new ecostratigraphic relations for the region are indicated, such as the last common occurrence of Dictyocha brevispina at 2.6 - 3.0 m.y. ago during a cool interval. Elements of North Pacific and low-latitude biostratigraphic zonations can be identified, but the mixing of cool- and warm-indicator taxa prompted the definition of the new Miocene Mesocena hexalitha Subzone and Pliocene Distephanus jimlingii Subzone. Scanning-electron microscope study of Leg 86 silicoflagellates was done to determine whether various types of skeletal surface texture are temperature dependent. To conduct the study we organized a new surface-texture descriptive code, which characterizes the apical structure/basal ring/spine sequence using new definitions of the terms crenulate (C), linear (L), nodular (N), reticulate (R), and smooth (S). One new silicoflagellate genus, Caryocha Bukry et Monechi, n. gen., is described and several new combinations are made.

Cretaceous calcareous nannofossils of DSDP Leg 77 holes

Five of the six sites drilled during Leg 77 of the Deep Sea Drilling Project yielded Cretaceous sediments. Two of these sites, 535 and 540, form a composite section that spans the upper Berriasian through most of the Cenomanian. Olive black marly limestones in this interval yield relatively rich, well-preserved nannofossil assemblages that allow biostratigraphic subdivision of the sequence. This composite section provides important information on the Early Cretaceous history of the Gulf of Mexico, as well as additional information on tropical Lower Cretaceous nannofossil assemblages. The post-Cenomanian nannofossil (and sedimentary) record is limited to a thin, condensed section of Santonian through lower Maestrichtian pelagic sediments at one site (538) and is absent or represented by redeposited material at the other sites. Two new genera, Perchnielsenella and Darwinilithus, are described. Two new taxa, Darwinilithus pentarhethum and Lithraphidites acutum ssp. eccentricum, are described; and two new combinations, Rhagodiscus reightonensis and Perchnielsenella stradneri, are propose.

Calcareous dinoflagellates in Cretaceous to Recent sediments of DSDP Hole 39-356

Calcareous dinoflagellates often dominate the dinoflagellate cyst assemblage in Cretaceous to Recent oceanic sediments. However, their distribution in Paleogene sediments has scarcely been studied. The investigation of samples from DSDP Site 356 for their calcareous dinoflagellate content revealed 35 mainly long-ranging taxa. The associations and characteristic wall types (pithonelloid, oblique, radial, tangential) fluctuate quantitatively and qualitatively in distinct stratigraphic patterns. Significant shifts, primarily at the K/T boundary and the Paleocene/Eocene boundary, reflect changes in environmental conditions. Certain dinoflagellates forming calcareous cysts, such as Operculodinella operculata, were well adapted to the relatively rapid change of environmental conditions at the K/T boundary, thus blooming to dominate the carbonate flux to the ocean floor. In contrast to the stable Paleocene associations, Eocene calcareous dinoflagellates show fluctuations in relative abundances. These fluctuations can possibly be attributed to redeposition related to increased seaward transport of specimens, due to strengthened western boundary currents. The flora includes two new genera, one new species, and two new forms: Retesphaera diadema Hildebrand-Habel, Willems et Versteegh, gen. et. sp. nov., Cervisiella saxea (Stradner, 1961) Hildebrand-Habel, Willems et Versteegh, gen. et comb. nov., Sphaerodinella? tuberosa forma elongata Hildebrand-Habel, Willems et Versteegh, comb. et forma nov., Sphaerodinella? tuberosa forma variospinosa Hildebrand-Habel, Willems et Versteegh, comb. et forma nov. Three new combinations are proposed: Cervisiella saxea (Stradner, 1961) Hildebrand-Habel, Willems et Versteegh, gen. et comb. nov., Operculodinella operculata (Bramlette et Martini, 1964) Hildebrand-Habel, Willems et Versteegh, comb. nov., and Sphaerodinella? tuberosa (Kamptner, 1963) Hildebrand-Habel, Willems et Versteegh, comb. nov. The genus Operculodinella Kienel, 1994 is emended.

Eocene siliceous and calcareous phytoplankton, Deep Sea Drilling Project Holes 95-612 and 95-613

Eocene siliceous and calcareous phytoplankton, with emphasis on silicoflagellates, were studied in 62 samples from DSDP Sites 612 and 613 on the continental slope and rise off New Jersey. The mid-latitude assemblages correlate well with assemblages from California, Peru, and offshore of southern Brazil, but are distinctly different from high-latitude cold-water assemblages of the Falkland Plateau off southern Argentina. Coccoliths and silicoflagellates provide evidence for the presence of a fairly complete middle and upper Eocene sequence, represented by a composite of Sites 612 and 613. A major unconformity occurs at the middle Eocene to upper Eocene contact at Site 612. The genus Bachmannocena Locker is emended and proposed as a replacement for genus Mesocena Ehrenberg for ring silicoflagellates. Six new silicoflagellates and one new diatom are described: Bachmannocena apiculata monolineata Bukry, n. subsp., Corbisema amicula Bukry, n. sp., C. bimucronata elegans Bukry, n. subsp., C. hastata incohata Bukry, n. subsp., C. jerseyensis Bukry, n. sp., Dictyocha acuta Bukry, n. sp., and Coscinodiscus eomonoculus Bukry, n. sp. Also, one new replacement name, B. paulschulzn Bukry, nom. nov., and 24 new combinations are proposed for genus Bachmannocena.

Calcareous nannofossil biostratigraphy of the central East Pacific Rise

During Leg 92 of the Deep Sea Drilling Project, sediments containing calcareous nannofossils of latest Oligocene to Holocene age were recovered from 14 holes at six sites (597 to 602) along the East Pacific Rise. The combined sections yield a virtually complete record for the region, with a compressed upper Miocene to Pleistocene interval. The nannofossil content of 14 U.S.N.S. Eltanin piston cores from the study area were also examined in order to supplement data generated during Leg 92. Two taxonomically new combinations are presented: Sphenolithus umbellus and Pontosphaera segmenta. Assemblages of calcareous nannofossils juxtaposed in reversed stratigraphic order within the upper Miocene provide strong evidence for downslope transport of sediments along the East Pacific Rise during the Messinian. Narrow bands of dark metalliferous sediment of coccolith Zone CN8b alternate with normal light-colored, in situ, pelagic sequences of Zone CN9b. This may indicate more vigorous bottom current activity between 5.40 and 6.70 Ma.

Diatom abundances in ODP Leg 114 holes

The practically continuous, paleomagnetically dated late Gauss-Brunhes sediment profiles of ODP Sites 699 and 701, south of the present Polar Front Zone (PFZ), and Site 704, north of the present PFZ, are used for a high-resolution study of abundance fluctuations of eight stratigraphic marker species in space and time. Ecological restrictions and preferences of the diatom species Hemidiscus karstenii, Actinocyclus ingens f. planus, Thalassiosira elliptipora, Thalassiosira kolbei, Thalassiosira vulnifica, Simonseniella barboi, Cosmiodiscus insignis, and Nitzschia weaveri are deduced. The ages of their first abundant appearance datums (FAAD), last-appearance datums (LAD), and last abundant appearance datums (LAAD) at the three sites are determined. The interpolated datum ages agree relatively well with those determined by other authors, if one interprets most of their LADs as LAADs. FAADs and LAADs produce more accurate datums than LADs. For the late Matuyama (younger than approximately 2.0 Ma), when PFZ fluctuations effected all three site sites, the datum ages determined agree within the methodically caused limits of accuracy for each datum. For the early Matuyama (older than approximately 2.0 Ma) the results can be interpreted as either that the ages of the FAAD of T. kolbei and LAAD of T. vulnifica datums determined at Sites 699 and 701 are more reliable or that these datums are diachronous between these two sites and Site 704. Such a diachroneity could be caused by different paleoceanographic conditions (stable subantarctic conditions over Site 704 and stable antarctic conditions over Sites 699 and 701). A few taxonomic changes were necessary. One new genus is defined (Simonseniella gen. nov.) and five new combinations are proposed: Simonseniella barboi (Brun) comb, nov., Simonseniella praebarboi (Schrader) comb, nov., Simonseniella curvirostris (Jousé) comb, nov., Thalassiosira elliptipora (Donahue) comb, nov., and Thalassiosira vulnifica (Gombos) comb. nov.

Oligocene-Miocene calcareous nannofossils in ODP Leg 149 holes

During Ocean Drilling Program (ODP) Leg 149, five sites were drilled on the Iberia Abyssal Plain in the northeastern Atlantic Ocean. Both Mesozoic and Cenozoic sediments were recovered. Oligocene to Miocene sediments were cored at deepwater Sites 897, 898, 899, and 900. Except for a few intervals, occurrences of generally abundant and well-preserved calcareous nannofossils suggest that the deposition of the turbidite-type sediments occurred above the calcite compensation depth (CCD). One major unconformity in the middle late Miocene is present. Detailed quantitative analyses of calcareous nannofossils are used to determine the changes occurring among the nannoflora in relation to sea-level variation. A succession of 89 biohorizons from the early Oligocene to the late Miocene are defined by combining the biostratigraphic results of the four sites studied in the Iberia Abyssal Plain. One new genus and eight new species are described: Camuralithus, Camuralithus pelliculatus, Ericsonia detecta, Helicosphaera limasera, Sphenolithus akropodus, Sphenolithus aubryae, Sphenolithus cometa, Reticulofenestra circus, and Syracosphaera lamina. Two new variations and seven new combinations are also introduced.

Stratigraphic distribution of marine palynomorph species recorded for the Miocene of ODP Hole 105-645E (Table 1)

A total of 145 samples were analyzed for palynology, and all were found to be productive. Residues are dominated by pollen, terrestrial spores, and land plant tissues. Marine palynomorphs occur in all samples, which allowed us to recognize five Miocene dinocyst assemblage zones. Dinocyst assemblages indicate cool-water conditions and suggest a neritic rather than fully oceanic environment, with not only North Atlantic and Norwegian Sea affinities, but also containing both notable protoperidiniacean and possible endemic elements. Dinocyst assemblages indicate an early Miocene age for the bottom of Hole 645E and an age no younger than early late Miocene (Sample 105-645E-24R, CC) near the top of the interval studied. These age assignments provide an estimated initiation of ice rafting in Baffin Bay at between 7.4 and 9.5 Ma. Increased terrigenous influx and apparent disappearance of certain dinocyst taxa occur in the middle to late Miocene and may be related to oceanographic changes or climatic deterioration. Spores and pollen indicate a climate that varied within a temperate regime during the early and middle to early late Miocene, followed by climatic deterioration. Four new dinocyst species are described: Batiacasphaera gemmata, Impletosphaeridium prolatum, Operculodinium vacuolatum, and Selenopemphix brevispinosa. The acritarch genus Cyclopsiella Drugg and Loeblich is emended, and two new combinations have been created: Cyclopsiella granosa (Matsuoka) and Cyclopsiella? laevigata (Chateauneuf). Cyclopsiella granosa (Matsuoka) n. comb. is considered a subjective junior synonym of Cyclopsiella granulata He and Li. Ascostomocystis granulatus Chateauneuf has been provisionally allocated to Cyclopsiella and renamed Cyclopsiella? chateauneufii. Two new acritarch species are described: Cyclopsiella spiculosa and Cymatiosphaera! baffinensis.

Eocene-Oligocene diatoms in the western Indian Ocean

The occurrence of diatom species in the Eocene-Oligocene sections of Ocean Drilling Program (ODP) Leg 115 sites and Deep Sea Drilling Project (DSDP) Sites 219 and 236 in the low-latitude Indian Ocean are investigated. Diatoms are generally rare and poorly preserved in the Paleogene sequences we studied. The best-preserved assemblages are found close to ash layers in early Oligocene sediments. The low-latitude diatom zonation established for the Atlantic region by Fenner in 1984 is fully applicable to the Paleogene sequences of the western Indian Ocean. Correlation of the diatom zones to the calcareous nannofossil stratigraphy of the sites places the Coscinodiscus excavatus Zone of Fenner within calcareous nannofossil Subzone CP16b. For the Mascarene Plateau and the Chagos Ridge, the times when the sites studied, together with the areas upslope from them, subsided to below the euphotic zone are deduced from changes in the relative abundance between the group of benthic, shallow-water species and Grammatophora spp. vs. the group of fully planktonic diatom species. The Eocene section of Site 707, on the Mascarene Plateau, is characterized by the occurrence of benthic diatoms (approximately 10% of the diatom assemblage). These allochthonous diatoms must have originated from shallow-water environments around volcanic islands that existed upslope from ODP Site 707 in Eocene times. In Oligocene and younger sediments of Sites 707 and 706, occurrences of benthic diatoms are rare and sporadic and interpreted as reworked from older sediments. This indicates that the area upslope from these two Mascarene Plateau sites had subsided below the euphotic zone by the early Oligocene. Only Grammatophora spp., for which a neritic but not benthic habitat is assumed, continues to be abundant throughout the Oligocene sequences. The area of the Madingley Rise sites (Sites 709-710) and nearby shallower areas subsided below the euphotic zone already in middle Eocene times, as benthic diatoms are almost absent from these Eocene sections. Only sites located on abyssal plains, and which intermittently received turbidite sediments (e.g., Sites 708 and 711), contain occasionally single, benthic diatoms of Oligocene age. The occurrence of the freshwater diatom Aulacosira granulata in a few samples of late early Oligocene and late Oligocene age at Sites 707, 709, and 714 is interpreted as windblown. Their presence indicates at least seasonally arid conditions for these periods in the source areas of eastern Africa and India. Three new species and two new combinations are defined: Chaetoceros asymmetricus Fenner sp. nov.; Hemiaulus gracilis Fenner, sp. nov.; Kozloviella meniscosa Fenner, sp. nov.; Cestodiscus demergitus (Fenner) Fenner comb, nov.; and Rocella princeps (Jouse) Fenner comb. nov.