The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer

Background: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. Methods: The toxicity of aspirin and aspirin derivatives to OC and a colorectal cancer (CRC) cell line were investigated in the presence and absence of platins. Results: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 CRC cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. Conclusion: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p </= 5 x 10). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1x10) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 x 10) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10); rs1229984-ADH1B, p = 7 x 10; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility

Morfologia externa dos cicadellinae (homoptera, cicadellidae): comparação entre versigonalia ruficauda (walker) (cicadellini) e tretogonia cribrata melichar (proconiini), com notas sobre outras espécies e análise da terminologia External morphology of the cicadellinae (homoptera, cicadellidae): comparison between versigonalia ruficauda (walker) (cicadellini) and tretogonia cribrata melichar (proconiini), with notes on other species and an analysis of the structural terminology

<abstract language="eng">The external morphology of two cicadelline species, Versigonalia ruficauda (Walker, 1851) (Cicadellini) and Tretogonia cribrata Melichar, 1926 (Proconiini), is analyzed. The head, axillary sclerites, wing venation, female genitalia, and tegumentary processes are described. Notes on other Cicadellini - Amblyscarlidia albofasciata (Walker, 1851), Tettisama quinquemacidata (Germar, 1821), Macugonalia lencomelas (Walker, 1851), and Diedrocephala variegata (Fabricius, 1775) - and Proconiini - Ciccus adspersus (Fabricius, 1803), Homoscarta superciliaris (Jacobi, 1905), Ichthyobelus sp., and Rhaphirrhinus phosphoreus (Linnaeus, 1758) - are added. A technique for dissecting the female genitalia is presented. The facial porlion of head in V. ruficauda, T. cribrata, and remaining species has a large sclerite (frons or postfrontofrons) clearly defined by the frontogenal suture. Below the frons, and separated from it by the epistomal suture, a smaller sclerite is present (clypeus). The identification of these sclerites is based on comparisons with descriptions in the literature of a generalized Pterygota, a Psocoptera, a fossil Hemipteroidea, and other Homoptera. The conclusions about the identities of frons and clypeus corroborate the hypotheses of Hamilton (1981) on the homologies of cephalic areas in Rhynchota. The facial sclerites have modifications related with the xyleniomyzous diet. The frons is swollen, providing a larger area for attachmcnt of cibarial muscles. Other modifications increasing the area of frons are observed in the Proconiini. In C. adspersus its lateral margins are distinctly pronounced and its upper portion has a pair of lateral elevations. In Ichthyobelus sp. and R. phosphoreus the upper part of frons is greatly developed, occupying 4/5 of dorsal area of head on middle line. The vertex is limited to a small portion (1/5) of that area. The clypeus is also swollen, a fact related with the greater development of cibarium. This character is more conspicuous in the Proconiini. In this tribe the clypeus has a convex projection occupied by the cibarium, which is greatly devcloped. The pronotum and forewings in T. cribrata are covered by pits, each with a seta on external margin. These pits are similar (and maybe homologous) to struetures in the abdomen of a membracid (Goniolomus tricomiger Stål. 1869). The pronotum is smooth in V. ruficauda. However, pits similar to those of T. cribrata, although smaller. oceur near the forewing veins. A strong costal vein is present in the forewings of the 10 studied species. This vein is formed by a fusion between precosta (PC), costa anterior (CA), and costa posterior (CP). Vestiges of subcosta posterior (ScP) and media (M) occur in the forewing base. A vein formed by a fusion between anal (A) and jugal (J) veins is observed along the inner margin of clavus. In the hindwings, PC, CA, and CP are also fused. The occurrence of PC can be inferred by the presence of the wing coupling lobe. which represents its final part. Jugal anterior (JA) is fused to anal posterior (AP"). Jugal posterior (JP) occurs as a small rudiment at hindwing base. The characters of fore - and hindwings confirm the observations of Dworakowska (1988) on the Cicadellidae. The presence of PC and J corroborates Kukalová-Peck's (1983) model of the primitive pterygote venation. Comparisons between the Cicadellinae and a description of a fossil species of the order Diaphanopterodea (Kukalová-Peck 1992) revealed remarkable similarities in female genitalia. Such similarities (manifested in the positions of gonocoxites eight and nine, gonangulum, valvulae eight and nine, and lergite nine) permit a correct interpretation of the genital structurcs in the subfamily. The sclerites of the genital chamber described by Young (1977) in females of various Cicadellini are the reduced eighth abdominal sternite. Sclerotized plates in this sternite occur in A. albofasciata, T. quinquemaculata, T. cribrata, C. adspersus, and H. superciliaris. Comparisons carried out among these Cicadellinae, allied with data from the literature, indicate that the eighth sternum can provide useful characters for the subfamily taxonomy. Features of potential taxonomic interest in valvulae eight and nine include tegumentary processes (valvulae eight), shaft form, and teeth form and distribution (valvulae nine). Lists with the terms suggested for head, wings, and female genitalia are included, together with synonyms proposed by other taxonomists and morphologists