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Summary Animal-type melanoma (ATM) represents a rare subtype within the wide spectrum of melanocytic tumors. Clinically, ATM lesions appear as sharply demarcated, brown, black and dark blue pigmented nodules, which show grey-white surface elements on dermatoscopy. The tumor is restricted to the dermis and arranged in irregular fascicles, which are composed of spindle-shaped and epithelioid melanocytes. Moderate tumor cell pleomorphism, mitoses and apoptotic cells all suggest a malignant process. Abundant, finely dispersed melanin pigment within tumor cells as well as numerous melanophages are strongly suggestive of ATM. Even though locoregional lymph node metastases are frequently found at diagnosis, the course of ATM is generally benign. Specific molecular changes may be detected in melanocytes from lesions and lymph nodes on fluorescence in situ hybridization (FISH). Such findings strongly indicate the malignant potential of ATM. The peculiar biology of ATM, as a moderately malignant tumor, is reflected in a new histopathological classification within the spectrum of dermal borderline melanocytic tumors (BMT).

BACKGROUND: Atypical teratoid/rhabdoid tumors are highly malignant embryonal central nervous system (CNS) tumors that were defined as an entity in 1996. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Atypical teratoid/rhabdoid tumors display a complex histomorphology, which renders them prone to misdiagnosis. They occur predominantly in young children, with an estimated prevalence of 1% to 2% among all pediatric CNS tumors. However, population-based data on the incidence of these tumors are not yet available. METHODS: A nation-wide survey of malignant high-grade CNS tumors (World Health Organization grade III/IV), diagnosed in children (aged birth to 14 years) from 1996 to 2006 was conducted by the Austrian Brain Tumor Registry. A central histopathology review was performed including the assessment of SMARCB1 (INI1) protein status. RESULTS: A total of 311 newly diagnosed, malignant CNS tumors were included. Atypical teratoid/rhabdoid tumors constituted the sixth most common entity (6.1%), referring to an age-standardized incidence rate of 1.38 per 1,000,000 person-years in children. Peak incidence was found in the birth to 2 years age group, where they were as common as CNS primitive neuroectodermal tumors and medulloblastomas. A total of 47.4% of atypical teratoid/rhabdoid tumors were initially diagnosed, whereas 52.6% were retrospectively detected by the central review. The 5-year survival of atypical teratoid/rhabdoid tumor patients was 39.5%, with 66.7% in the correctly diagnosed group versus 15.0% in the not recognized group (P = .0469). CONCLUSIONS: Clinicians and pathologists should be aware of the high incidence of atypical teratoid/rhabdoid tumors in young children to optimize diagnostic and therapeutic management of patients with these tumors. Cancer 2010. © 2010 American Cancer Society.

Ovarian cancer arises mostly from the ovarian surface epithelium. The aim of our study was to compare the effects of cytokines in ovarian surface epithelial (OSE) cells and in ovarian carcinoma cells. Proliferation and expression of surface antigens (CA-125 and classes I and II antigens of the major histocompatibility complex [MHC]) were measured in OSE cells obtained from 7 different patients and 7 ovarian carcinoma cell lines. Proliferation of OSE cells remained unaffected by interferon (IFN)-α or IFN-γ, whereas interleukin-I (IL-I) and tumor necrosis factor (TNF) increased cell growth. Proliferation of ovarian carcinoma cells was reduced by both types of IFN as well as TNF but was not affected by IL-I. Expression of the tumor marker CA-125 was increased by IFN-γ in ovarian carcinoma cells but not by any other treatment. None of the cytokines affected CA-125 surface expression in OSE cells. Expression of MHC-I was augmented in OSE and in carcinoma cells by both IFNs but not by the other cytokines. Both types of cell were negative for MHC-II, but IFN-γ induced its expression in both OSE and carcinoma cells. Significant concentrations of the cytokines evaluated here have been measured in blood and follicular fluid by several authors. The different actions of these cytokines in OSE and carcinoma cells could therefore be important in understanding the role of such molecules in the regulation of physiological and pathological processes in the ovary, such as ovulation or malignant proliferation. © 1996 Wiley-Liss, Inc.

Testicular carcinoma in situ (CIS) is usually diagnosed histologically on surgical biopsies. The present study was performed to test an alternative approch—DNA flow cytometry (FCM) of testicular fine-needle aspirates (FNA)—for the detection of this lesion. FNAs from 18 cases of testicular germ cell tumors (TGCT) and tumor adjacent parenchyma were analysed by DNA FCM. DNA histograms of all cell nuclei and histograms representing selectively the hyperdiploid compatment were analysed. The presence and extention of CIS were determined by histology and immunohistochemistry. In 16 to 18 cases, CIS was histologically present, whereas aneuploid peaks were detected in only 11 cases in DNA histograms of all cell nuclei. In the analysis of the histograms of the hyperdiploid region, 4 additional cases of CIS could be identified increasing the sensitivity to 15/16 cases (93.8%). In all but one case, the DNA indices of CIS and invasive tumors were identical. The study demonstrates that DNA FCM of testicular FNAs using the described data acquisition and analysis could also be applicable for detection of CIS in a clinical situation. © 1994 Wiley-Liss, Inc.

Tumor-cell extravasation involves sequential adhesive interactions with vascular endothelium and the subendothelial basement membrane. We have established a 3-dimensional model in vitro to simulate these events and to elucidate targets of the anti-cell-adhesive synthetic peptide RGDS. Tumor spheroids of the melanoma cell line ST-ML-12 served as models of tumor-cell emboli and were transferred onto human umbilical vein endothelial cells. To imitate the vascular anatomy, the latter were grown on reconstituted basement membranes produced by dextran-stimulated bovine corneal endothelial cells. RGDS did not affect the homotypic aggregation of the tumor cells and only minimally inhibited the attachment of the spheroids to the reconstituted vessel. A short-term (20 min) inhibition of adhesion to denuded basement membranes was observed. The attachment was closely associated with damage to the endothelial cells by oxygen-derived free radicals. RGDS retarded endothelial injury for up to 3 hr. The most prominent effect was observed after penetration of the endothelium. RGDS suppressed the emigration of tumor cells from the attached tumor-cell cluster in a dose- and time-dependent fashion. After 12 hr, the inhibitory effect progressively declined. This was not due to loss of activity of the peptide, indicating a resistance mechanism in the melanoma cells. On purified components of the basement membrane, RGDS effectively inhibited the initial spheroid attachment to fibronectin and collagen IV but had no effect on attachment to laminin. By contrast, subsequent migration was significantly suppressed on all substrata. Our model permits the study of dynamic cell-cell and cell-extracellular-matrix interactions and indicates that RGDS might predominantly act on early tumor-cell locomotion after penetration of the endothelium.

In 1- und 4-Stellung geeignet substituierte 2-Aza-1,3-butadiene (z.B. 5) reagieren mit Acrylnitril nicht nach Diels-Alder, sondern fuhren in einer Michael-Addition zu 5-(1-Alkenylimino)-4,4-dialkylpentannitrilen (z. B. 8), die sich durch hydrierende Cyclisierung in 1,3,3-Trialkylpiperidine (9) umwandeln lassen. Die gleichen Piperidine sind auch durch Cyclisierung der Azomethine 4 von 4,4-Dialkyl-4-formylbutannitrilen zuganglich. A New Synthesis of N-Alkylated 3,3-Dialkylpiperidines In 1- and 4-position suitably substituted 2-aza-1,3-butadienes (e.g. 5) do not react with acrylonitrile according to a Diels-Alder reaction but in a Michael addition to give 5-(1-alkenylimino)-4,4-dialkylpentanenitriles (e.g. 8), which can be transformed into 1,3,3-trialkylpiperidines (9) by hydrogenating cyclization. The same piperidines are also obtained by cyclization of the azomethines 4 of 4,4-dialkyl-4-formylbutanenitriles.

The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization. Forty-seven (75%) of the tumors contained a Ki-ras mutation at codon 12. No predominant amino acid substitution or nucleotide transition at this codon was observed. Two carcinomas exhibited 2 distinct Ki-ras mutations. No particular correlation could be established between the incidence of Ki-ras mutation and clinical parameters (sex, age, survival), tumor grade or tumor stage.

Die Behandlung von Braunkohlenschwelteer-Destillaten mit 96,8%iger Flussaure ergibt Schmierole und Dieselkraftstoffe. Die Abhangigkeit der Reaktionsergebnisse von Sauremenge, Zeit und Temperatur werden studiert und Vergleichsversuche mit Schwefelsaure durchgefuhrt.

Durch oxydativen Abbau von Telodrin® zur 1.2.3.4.7.7-Hexachlor-bicyclo[2.2.1]hepten-(2)-dicarbonsaure-(5.6) (3) wird die endo-Konfiguration des anellierten 5-Ringes bewiesen. Weitere ohne Inversion verlaufende nucleophile sowie elektrophile Umsetzungen vom Friedel-Crafts-Typ beweisen, das die beiden Chloratome in 1.3-Stellung den Wasserstoffatomen in 8- und 9-Stellung entsprechend der Formel 2i gleichgerichtet sind. 1H-NMR-Spektroskopische Untersuchungen stutzen diese Ergebnisse.

Durch Behandlung von 4.5.6.7-Tetrachlor-10.10-dihydroxy-bzw. 4.5.6.7-Tetrachlor-10.10-diathoxy-4.7- methylen-4.7.8.9-tetrahydro-phthalan, 1.4.5.6-Tetrachlor-7.7dimethoxy-2.3-bis-hydroxymethyl- bicyclo[2.2.1]hepten-(5), dessen Diacetat oder cyclischem Sulfit mit konz. Schwefelsaure wird das 4.5.6.7-Tetrachlor-10.10- dihydroxy-4.7-methylen-4.7.8.9-tetrahydro-phthalanhydrat erhalten, das durch partielle Dehydratisierung in das Ketonhydrat und in das 4.5.6.7-Tetrachlor-4.7-methylen-4.7.8.9- tetrahydro-phthalanon-(10) ubergeht.

Die Behandlung einer Reihe α-substituierter Carbonsauren mit wasrigen Ammoniumpolysulfidlosungen bei 180 ± 5° unter Druck fuhrt zu den um ein C-Atom niedrigeren Carbonsaureamiden. Der Reaktionsmechanismus wird diskutiert.

Bei der Chlorierung von Dimethyl-, symm. Dichlordimethyl- und Tetrachlordimethylsulfid wurden Chloroform, Thiophosgen, Penta- und Hexachlordimethylsulfid aufgefunden. Fur das Tetrachlordimethylsulfid wurden physikalisch-chemische Konstanten festgelegt. Als Hydrolyseprodukt konnte Trithioformaldehyd nachgewiesen werden. Bei der Chlorierung von Perchlormethylmercaptan in der Kalte im UV-Licht wurden Tetrachlorkohlenstoff u. Schwefeldichlorid, beim Zerfall im UV-Licht Thiophosgen, Tetrachlorkohlenstoff und Schwefelmonochlorid gefunden. Das nur bedingt stabile Penta- und Hexachlordimethylsulfid konnten angereichert und durch ihre Zerfallsprodukte nachgewiesen, aber aus einem Gemisch mit Perchlormethylmercaptan und Tetrachlorkohlenstoff nicht rein isoliert werden.

Reaktionen an 1-substituierten 4.5.6.7.10.10-Hexachlor-4.7-methylen-4.7.8.9-tetrahydro -phthalanen mit Benzol unter Einwirkung von Eisen(III)-chlorid oder Aluminiumchlorid fuhren — abhangig von der Wahl des eingesetzten Substituenten und Katalysators — zu 4.5.6.7.10.10-Hexachlor-1-phenyl-4.7-methylen-4.7.8.9-tetrahydro-phthalan oder unter offnung des heterocyclischen Ringes zu 1.2.3.4.7.7-Hexachlor-5-hydroxymethyl-6-benzhydryl-bicyclo [2.2.1]-hepten-(2).

Durch Addition von 2.5-Dihydro-furan an Tetrachlorfuran werden im Gegensatz zur Addition an Hexachlorcyclopentadien die endo- und exo-Form des 4.5.6.7-Tetrachlor-4.7-epoxy-4.7.8.9-tetrahydro-phthalans (3) erhalten. Die Zuordnung der endo- und exo-Konfiguration durch chemisch-biologische Untersuchungen wird durch 1H-NMR-Spektroskopie bestatigt.

Uber das durch Bromierung von 4.5.6.7.10.10-Hexachlor-4.7-methylen-4.7.8.9-tetrahydro-phthalan (1) zugangliche 1-Bromid 2 fuhren Reaktionen mit Alkoholen, Phenol und Mercaptanen zu inneren Halbacetalen und Halbmercaptalen 3 des 1.4.5.6.7.7-Hexachlor-2-hydroxy-methyl-bicyclo[2.2.1]hepten-(5)-aldehyds-(3). Mit Pyridinen lassen sich entsprechende Pyridiniumbromide 4 gewinnen. Die 1-Amino-Derivate 9 und 10 resultieren aus dem durch Hydrolyse des 1-Bromids mit Protonenfangern gewonnenen 4.5.6.7.10.10-Hexachlor-1-hydroxy-4.7-methylen-4.7.8.9-tetrahydro-phthalan (5) durch Kondensation mit aromatischen Aminen und α-Aminocarbonsaureestern.

Durch Sulfochlorierung lassen sich aus den Hydrochloriden des n-Propyl-, Isobutyl- und n-Butylamins praparative Mengen einheitlicher Aminoalkan-sulfo-chlorid-hydrochloride gewinnen. Die Konstitution der Hydrochloride wird durch Cyclodehydrochlorierung zu Sultamen und anschliesende Hydrochlorolyse unter Ringoffnung bewiesen.