Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts

Background: Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. Materials and methods: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. Results and conclusion: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab′)2 fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras statu

The Diversity and Abundance of Small Arthropods in Onion, Allium cepa, Seed Crops, and their Potential Role in Pollination

Onion, Allium cepa L. (Asparagales: Amaryllidaceae), crop fields grown for seed production require arthropod pollination for adequate seed yield. Although many arthropod species visit A. cepa flowers, for most there is little information on their role as pollinators. Small flower visiting arthropods (body width < 3 mm) in particular are rarely assessed. A survey of eight flowering commercial A. cepa seed fields in the North and South Islands of New Zealand using window traps revealed that small arthropods were highly abundant among all except one field. Insects belonging to the orders Diptera and Thysanoptera were the most abundant and Hymenoptera, Collembola, Psocoptera, Hemiptera, and Coleoptera were also present. To test whether small arthropods might contribute to pollination, seed sets from umbels caged within 3 mm diameter mesh cages were compared with similarly caged, hand-pollinated umbels and uncaged umbels. Caged umbels that were not hand-pollinated set significantly fewer seeds (average eight seeds/umbel, n = 10) than caged hand-pollinated umbels (average 146 seeds/umbel) and uncaged umbels (average 481 seeds/umbel). Moreover, sticky traps placed on umbels within cages captured similar numbers of small arthropods as sticky traps placed on uncaged umbels, suggesting cages did not inhibit the movement of small arthropods to umbels. Therefore, despite the high abundance of small arthropods within fields, evidence to support their role as significant pollinators of commercial A. cepa seed crops was not found

Macroevolutionary Patterns in the Aphidini Aphids (Hemiptera: Aphididae): Diversification, Host Association, and Biogeographic Origins

, the most diverse genus in the family. We used a combined dataset of one nuclear and four mitochondrial DNA regions. A molecular dating approach, calibrated with fossil records, was used to estimate divergence times of these taxa.Most generic divergences in Aphidini occurred in the Middle Tertiary, and species-level divergences occurred between the Middle and Late Tertiary. The ancestral state of host use for Aphidini was equivocal with respect to three states: monoecy on trees, heteroecy, and monoecy on grasses. The ancestral state of Rhopalosiphina likely included both heteroecy and monoecy, whereas that of Aphidina was most likely monoecy. The divergence times of aphid lineages at the generic or subgeneric levels are close to those of their primary hosts. The species-level divergences in aphids are consistent with the diversification of the secondary hosts, as a few examples suggest. The biogeographic origin of Aphidini as a whole was equivocal, but the major lineages within Aphidina likely separated into Nearctic, Western Palearctic, and Eastern Palearctic regions.Most generic divergences in Aphidini occurred in the Middle Tertiary when primary hosts, mainly in the Rosaceae, were diverging, whereas species-level divergences were contemporaneous with diversification of the secondary hosts such as Poaceae in the Middle to Late Tertiary. Our results suggest that evolution of host alternation within Aphidini may have occurred during the Middle Tertiary (Oligocene) when the secondary hosts emerged

Pest management of the New Zealand flower thrips Thrips obscuratus (Crawford) (Thysanoptera: Thripidae) on stonefruit in Canterbury, New Zealand

The New Zealand flower thrips (Thrips obscuratus (Crawford)) is an important pest of stonefruit during flowering and at harvest in New Zealand. The biology and control of this species formed the basis for this study. A simple method for laboratory rearing is described that facilitated studies on the bionomics of T. obscuratus. Aspects of reproduction, fecundity, requirements for oviposition and development, development rates, temperature thresholds, thermal constants, and lifespan are detailed. T. obscuratus has been reported from at least 223 endemic and introduced plant species. Larvae were taken from 49 species around Canterbury. Adults were usually found on flowers but were also common on leaves and fruits. All larvae were on flowers except for two records from the fruit of stonefruit. The number and species of thrips infesting sprayed and unsprayed stonefruit flowers and fruit were determined. Adults and larvae were almost all T. obscuratus and adults were mostly female. Adults and larvae of thrips were found in stonefruit flowers from pink to shuck fall. Adults were found in similar numbers throughout flower development. Larvae were almost entirely absent at pink; numbers were small at full bloom and peaked at or just after petal fall. Thrips adults, eggs and larvae were all common on peaches, nectarines and apricots. Thrips were most numerous on ripe fruit, although they were found on fruit for the local market up to three weeks before harvest. Thrips numbers were highest on stonefruit varieties ripening during December and January and lowest on varieties ripening during February, March and April, and were higher on peaches than apricots and nectarines. Sources of T. obscuratus infestations were probably from flowers in the vicinity of the orchard. Pupation sites for T. obscuratus were established as including the soil and litter beneath a flowering cabbage tree (Cordyline australis). Female T. obscuratus were parasitised and sterilised by a nematode thought to be Howardula aptini. Flying thrips were sampled inside and outside stonefruit blocks from September 1984 to August 1987. Several species including T. obscuratus, Thrips tabaci, Limothrips cerealium and Haplothrips niger were common. A broad pattern of the seasonal abundance of T. obscuratus was apparent from water trap samples. Thrips numbers were lowest in winter and low in spring, but increased gradually during summer. Numbers peaked in midsummer but declined suddenly in mid to late January. Numbers remained moderate to low throughout late summer and autumn. Seasonal abundance could be largely explained by the interrelationship of temperature, soil moisture and availability of host plants. Flight take-off thresholds of 15°C were established from weekly water trap samples for both male and female T. obscuratus adults. Both adults and larvae of T. obscuratus were found on hosts throughout the year, but were most common in early summer. There was no reproductive diapause for T. obscuratus females collected from the field in winter. In field experiments T. obscuratus males and females showed a preference for white without U.V., and to a lesser extent yellow, compared to green, blue, black and red. Traps baited with ethyl nicotinate caught significantly more T. obscuratus males and females than traps baited with anisaldehyde, benzaldehyde, peach juice, peach fruit and unbaited traps. An insecticide trial investigated the protection of nectarine flowers from thrips infestation and damage, using the insecticides fluvalinate or phosalone (low toxicity to bees) applied at full bloom as supplements to the current recommended spray programme. Thrips numbers were reduced, and export packout (based on russet only) was 10% higher for trees treated at full bloom than for those treated only with the recommended spray programme. Several varieties of ripe stonefruit picked at maturity for the local market and which had received only periodic applications of carbaryl were infested with adults, eggs and larvae. The application of low rates of fluvalinate for preharvest control of thrips on peach fruit was investigated. Peaches were sampled for thrips at local market maturity ('Redhaven') and export market maturity ('Flamecrest'). Low rates of fluvalinate (20% to 5% of field rates) reduced thrips infestation on both varieties. On 'Flamecrest' one application of fluvalinate at 10% field rate, 15 days before harvest, was more effective at reducing thrips infestation than the current recommended spray programme. . The management of T. obscuratus on stonefruit in Canterbury is reviewed in relation to previous research and knowledge gained from this study

Aspects of the biology and management of Froggatt's apple leafhopper (Typhlocyba Froggatti baker) in New Zealand

Froggatt's apple leafhopper (FALH) is a minor pest of apple in New Zealand although it has the potential to increase its pest status through insecticide resistance and any reduction of insecticide use aimed at 'key pests'. This thesis gathered basic biological information to rationalise any future management of this insect. Yellow sticky boards were used to sample FALH adults in three orchards under different management regimes and the adults of the egg parasite Anagrus armatus in two orchards. Sampling of overwintering eggs, summer eggs and nymphal instars occurred only in an abandoned orchard. Regular insecticide applications in a commercial orchard reduced the numbers of FALH and A. armatus to very low levels compared to those trapped in an abandoned orchard. All life stages of FALH sampled over two seasons in an abandoned orchard strongly suggested the presence of at least two, and possibly a partial third, generation. A similar temporal distribution was found in blackberry adjacent to an abandoned orchard. Overwintering eggs, summer eggs and nymphs showed no consistent preference for any of the examined positions within the tree. Adult numbers trapped on yellow sticky boards increased with height, due to a disproportionate increase of males with height in relation to females. The description of the pattern of distribution was established using the indices of Taylor's power law and Iwao's patchiness regression for overwintering eggs (randomly dispersed, cohesive groups of eggs), for two seasons of summer eggs (a clumped distribution with a basic component of individuals in both seasons) and two seasons of nymphal instars (basically random or clumped groups of individuals). Of the 27 distributions analysed, Taylor's power law gave the better data fit on 26 occasions. Only four distributions were described differently by the two models. FALH numbers built up quickly in a previously uninfested orchard through natural increase and migration. Migration over short distances was mainly influenced by the condition of the host plant and the prevailing wind. Conservative estimates of parasitism by A. armatus were established for overwintering FALH eggs (30-53%) and summer FALH eggs (20-100%) in an abandoned orchard. Yellow sticky board samples indicated that the life cycle of A. armatus was well synchronised with that of FALH. The appropriate base temperatures for different development stages of FALH were found to be between 9.7 and 11.0°C by laboratory studies and field measurement. A thermal constant of 463.5 ±10.5D° from egg to adult was established from laboratory studies. Acetate sheets placed on the yellow sticky boards only reduced the spectral reflectance by a small amount but improved sampling efficiency and trap storage. The yellow sticky boards were found to sample larger proportions of the FALH population in relation to the D-Vac (at all densities) and Johnson and Taylor suction trap (only at high densities). Sticky boards appeared to preferentially sample males in relation to females. Higher placement of sticky boards in the tree reduced the number of leafhoppers, other than FALH, caught. A rational approach to control, based on all available data for this insect, is discussed

Immunociblage des tumeurs: situation et perspectives en 2000

Following 15 years of experimental studies, tumor immunotargeting using monoclonal antibodies directed against tumor associated antigens shows now important monoclonal antibodies directed against tumor associated antigens shows now important clinical developments. This is mainly due to encouraging therapeutic results which have obtained using humanized antibodies such as the anti-CD20 rituximab in follicular B lymphomas and the anti-DrbB2 herceptin in breast carcinomas. Thanks to genetic engineering it is possible to graft variable or hypervariable regions from murine antibodies to human IgG, and even to obtain fully human antibodies by using either transgenic mice containing a large part of the human repertoire of human IgG, or selection of human antibody fragments expressed by phages. Radiolabeling of antibodies played a major role to demonstrate the tumor immunotargeting specificity and remains attractive for the diagnosis by immunoscintigraphy as well as for the treatment by radioimmunotherapy of some cancers. In this review, the current results and the prospects of diagnostic and therapeutic uses of anti-tumor antibodies and their fragments will be described. Concerning diagnosis, 123-iodine or 99m-technetium labeled Fab fragments allowed very demonstrative tumor images but this technique has a limited effect upon the therapeutic attitude. Immuno-PET (positron emission tomography) could enhance the sensitivity of this imaging method. Radio-immunoguided surgery and immunophotodetection are attractive techniques still under evaluation. Concerning therapy, 131-iodine labeled anti-CD20 antibodies gave spectacular results in non-Hodgkin's B lymphomas. In solid tumors which as less radiosensitive, radioimmunotherapy could concern small tumors and need the use of two-steps targeting and/or alpha emitters radioisotopes. Some other strategies will be described such as bispecific antibodies directed against tumors and immune effector cells, some antibody fragments expressed on T cells called T-bodies or some biological studies using intrabodies. Published data and works in progress demonstrate that immunotargeting of tumors will have a growing place in the treatments of cancer patients