Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

Introduction

Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.

Methods

75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).

Results

Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).

Conclusion

Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.     

Identification of glycosphingolipid receptors for pierisin-1, a guanine-specific ADP-ribosylating toxin from the cabbage butterfly

Pierisin-1, a cytotoxic protein found naturally in the cabbage butterfly, induces apoptosis of mammalian cells. Our recent studies suggest that pierisin-1 consists of an N-terminal ADP-ribosyltransferase domain, and a C-terminal region that binds to receptors on the surfaces of target cells and incorporates the protein into cells. The present study was undertaken to identify receptors for pierisin-1. The cross-linking and cloning experiments suggested that the proteins on cell membrane had no binding ability to pierisin-1. Inhibitory assays of fractionated lipids from human cervical carcinoma HeLa cells, which are highly sensitive to pierisin-1, indicated neutral glycosphingolipids on the cell surface to show receptor activity. Inhibitory assays and TLC immunostaining using anti-pierisin-1 antibodies demonstrated two neutral glycosphingolipids as active components. Analysis of their structures with glycosphingolipid-specific antibodies and negative secondary ion mass spectrometry identified them as globotriaosylceramide (Gb3) and globotetraosylceramide (Gb4). The receptor activities of Gb3 and Gb4 for pierisin-1 were also confirmed with these authentic compounds. Pierisin-1-insensitive mouse melanoma MEB4 cells were found to lack pierisin-1 receptors, including Gb3 and Gb4, but pretreatment of the cells with glycosphingolipid Gb3 or Gb4 enhanced their sensitivity to pierisin-1. Thus, Gb3 and Gb4 were proven to serve as pierisin-1 receptors. The C-terminal region of pierisin-1 consists of possible lectin domains of a ricin B-chain, containing QXW sequences, which are essential for its structural organization. Alteration of QXW by site-directed mutagenesis caused marked reduction of pierisin-1 cytotoxicity. Thus, our results suggest that pierisin-1 binds to Gb3 and Gb4 receptors at the C-terminal region, in a manner similar to ricin, and then exhibits cytotoxicity after incorporation into the cell.     

An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses

The compound Neu5Ac3alphaF-DSPE (4), in which the C-3 position was modified with an axial fluorine atom, inhibited the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolates examined. With the positive results obtained for inhibition of hemagglutination and hemolysis induced by A/Aichi/2/68 virus, the inhibitory effect of Neu5Ac3alphaF-DSPE (4) against MDCK cells was examined, and it was found that 4 inhibits the viral infection with IC50 value of 5.6 microM based on the cytopathic effects. The experimental results indicate that compound 4 not only inhibits the attachment of virus to the cell surface receptor but also disturbs the release of the progeny viruses from infected cells by inhibiting both hemagglutinin and sialidase of the influenza viruses. The study suggested that the compound is a new class of bifunctional drug candidates for the future chemotherapy of influenza.     

Increased nest predation in a declining and threatened Temminck's Stint Calidris temminckii population

We measured nesting success of the Temminck's Stint Calidris temminckii along the Finnish Bothnian Bay coast during 19 breeding seasons (1983–2001) and conducted a population census (1999–2002). We found 105 pairs, showing a marked decline from the previous survey (170 pairs 1987–95). Of the 424 'known-fate' nests, 47% hatched. Depredation caused 79.9% of the nest losses. Nesting failures increased from 1983–91 to 1992–2001 owing to a rise in nest predation. The proportion of failed nests that failed because of predation rose from 48.9 to 87.7%. When only depredated nests were considered as losses, Mayfield nest survival probability over the incubation period dropped from 69 to 31% (461 nests). This pattern emerged both in man-made and in natural habitats. Survival probability was independent of habitat type (natural vs. man-made). In an experiment involving videotaping of dummy nests, Common Gull Larus canus and Ruddy Turnstone Arenaria interpres were found to be the most important egg predators.     

Stomatal density, anatomy and nutrient concentrations of Scots pine needles are affected by elevated CO2 and temperature

Stomatal density, anatomy and nutrient concentrations of Scots pine (Pinus sylvestris L.) needles were studied during 3 years of growth at elevated CO₂ (693 ± 30 µmol mol⁻¹), at elevated temperature (ambient +2·8–6·2 °C depending on the time of the year) and in a combination of elevated CO₂ and temperature in closed-top chambers. The treatments were started in August 1996. At elevated temperature, the needles that were grown in the first year (i.e. the 1997 cohort) were thinner, had thinner mesophyll in the abaxial side, thinner vascular cylinder and lower stomatal density than those grown at ambient temperature. The proportion of mesophyll area occupied by vascular cylinder or intercellular spaces were not changed. Lower stomatal density apparently did not lead to decreased use of water, as these needles had higher concentrations of less mobile nutrients (Ca, Mg, B, Zn and Mn), which could indicate increased total transpiration. In the 1997 and 1998 cohorts, elevation of temperature decreased concentrations of N, P, K, S and Cu. In the 1999 cohort, contradictory, higher concentrations of N and S at elevated temperature may be related to increased nutrient mineralization in the soil. Elevation of CO₂ did not affect stomatal density, needle thickness, thickness of epidermis or hypodermis, vascular cylinder or intercellular spaces. Concentrations of N, P, S and Cu decreased at elevated CO₂. Reductions were transient and most distinct in the 1997 cohort. The effects of CO₂ and temperature were in some cases interactive, which meant that in the combined treatment stomatal density decreased less than at elevated temperature, and concentrations of nutrients decreased less than expected on the basis of separate treatments, whereas the thickness of the epidermis and hypodermis decreased more than in the separate treatments. In conclusion, alterations in the anatomy and stomatal density of Scots pine needles were more distinct at elevated temperature than at elevated CO₂. Both elevated CO₂ and temperature-induced changes in nutrient concentrations that partly corresponded to the biochemical and photosynthetic alterations in the same cohorts ( Luomala et al. Plant, Cell and Environment 26, 645–660, 2003 ) Reductions in nutrient concentrations and alterations in the anatomy were transient and more evident in the needle cohort that was grown in the first treatment year.     

PERCEIVED EATING DIFFICULTIES AND PREFERENCES FOR VARIOUS TEXTURES OF RAW AND COOKED CARROTS IN YOUNG AND ELDERLY SUBJECTS

The aim of the study was to determine how those texture attributes that elderly people find difficult to eat are related to their preferences for different modifications of carrot textures. This study was conducted with same methods in Finland and in the United Kingdom (UK). Trained sensory panels in both countries described sensory profiles of a range of carrot samples with same glossary of texture terms. The texture of carrot samples was manipulated using different preparation and cooking methods. Based on the Principal Component Analysis (PCA), boiled and puréed samples were perceived as soft, wet, pulpy and smooth, whereas raw samples were dry, brittle, rough, crispy and crunchy. Two age groups were used for the consumer tests: a young adult group aged 23 to 40 years, mean 32 (Finland) and 33 (UK) and an elderly group aged over 60 years, mean 75 (Finland) and 76 (UK). Both the elderly and young adult respondents considered samples as difficult to eat if they needed a long chewing time, were crunchy, hard, brittle, dry, rough or sharp, such as raw slices and coarsely grated samples. On the other hand, slimy, wet, smooth, soft and pulpy samples, such as boiled carrots and purée, were considered as easy-to-eat. The young adults liked more difficult textures such as rough, crispy, crunchy and hard than did the elderly respondents, but the easiest textures were not liked by either age group. Subjects with dental deficiencies liked easier textures more than those fully dentate.     

Insertion of the LINE retrotransposon MGL causes a conidiophore pattern mutation in Magnaporthe grisea

We obtained three Magnaporthe grisea morphological mutants that had the LINE transposon MGL inserted into the ACR1 locus. Sequence analysis revealed that ACR1 is homologous to medA, a developmental regulator of Aspergillus nidulans conidiation. These results demonstrated that MGL elements could transpose and cause insertional mutagenesis in M. grisea.