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.     

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.     

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.     

The effects of continuous illumination on the function and structure of Micrasterias torreyi Bail. (Conjugatophyceae)

Abstract. The division rate of Micrasterias torreyi cells grown under continuous illumination first accelerated but soon slowed down, and the cells lost their ability to divide after about 1 month. During the treatment the cells became pale green, the pyrenoids became fewer in number and defects appeared in the chloroplasts. After 1 month, the cells also soon died, even when subjected to intermittent illumination. The most striking structural alterations were found in the chloroplasts: the starch granules lost their typical structure, the lamellae were damaged and numerous electron dense precipitates appeared in the chloroplasts. The precipitates were similar to those formed in cells treated with supraoptimal external calcium concentrations and X-ray microanalysis showed that the precipitates were rich in calcium in both cases. The results suggest that light controls and activates the Ca²⁺ uptake in the plasma membrane as well as in the chloroplast envelope, that the large sized chloroplasts of Micrasterias are effective in regulation of cytoplasmic Ca²⁺ concentration, and that the injuries caused by continuous illumination may be largely due to the accumulation of Ca²⁺ in the chloroplasts.     

Novel mouse xenograft models reveal a critical role of CD4+ T cells in the proliferation of EBV-infected T and NK cells

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγ(null) strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases.     

Association between haematozoan infections and reproduction in the Pied Flycatcher

1. Parasites may affect breeding success of their host since they compete for the same resources as their hosts. Reproduction may also increase the susceptibility of a host to parasite infections owing to lowered resistance to parasites during breeding.
2. We studied the association between breeding performance and haematozoan parasite infection in the Pied Flycatcher ( Ficedula hypoleuca ) by using both natural data on reproduction and data from clutch size manipulations.
3. The most frequent blood parasites of the Pied Flycatcher in central Finland were Haemoproteus pallidus , Haemoproteus balmorali and Trypanosoma avium complex.
4. We did not find evidence that these haematozoan parasites have any debilitating effects on either reproduction or survival. The variation in reproductive effort did not seem to influence susceptibility to new blood parasite infections.
5. The intensity of Haemoproteus balmorali tended to increase in infected males as the brood size was artificially enlarged. Also, in females intensity of H. pallidus infection tended to increase with the level of clutch size manipulation. Thus, increased reproductive effort seems to debilitate the ability of Pied Flycatcher to control chronic infections.
6. Individuals with enlarged clutches/broods increased their reproductive effort at the expense of defence towards parasites. The cost of current reproduction may then be at least partly mediated by haematozoan infections.     

LIKING FOR ICE CREAM MEASURED WITH THREE PROCEDURES: SIDE-BY-SIDE, AFTER CONSUMPTION AND SINGLE SAMPLES

The purpose of this study was to compare how similar results are achieved by three different procedures of measuring liking for ice cream. Subjects (N=56) assessed their liking for three brands of vanilla ice cream on a 9-point scale in seven sessions within three weeks. The examined procedures were (1) tasting and rating all three brands simultaneously side-by-side within the same session, (2) rating each brand in separate sessions after ad libitum consumption and (3) tasting (without consumption) and rating each brand in separate sessions. The liking scores for brands differed significantly but the differences were small because all samples were well-liked. In all procedures, the ratings of liking differed clearly between those who ranked the brand first and those who ranked it second or third, even if there was a considerable number of tied first places. Correlations among the three different measurements of liking were relatively low for all brands of ice cream (r = 0.16 – 0.37). The most preferred brand for most respondents changed from one procedure to another. The perceived characteristics were close to ideal in all brands, and all three procedures gave similar mean results. The distance of mouthfeel, creaminess, sweetness, and vanilla aroma from ideal differed between those who liked the brand best and those who rated it second or third. These differences were larger in side-by-side and after consumption conditions compared to single sample presentation.     

Night,day, sunrise,sunset: do fish under snow and ice recognize the difference?

1. Although boreal lakes are ice‐covered for several months annually, little is known about the behaviour of fish under ice. To consider the reasons for diel vertical migrations (DVM) it is important to compare periods under ice as opposed to under open water. Echosounding provides a tool for non‐intrusive continuous monitoring of fish, even in winter. 2. Changes in the vertical distribution of fish through six 48‐h periods were monitored using a stationary, mounted echosounder that beamed vertically either from the bottom up or from the surface down from February to April, 2003. The up‐beaming and down‐beaming transducers were run alternately for 24 h each over the 48‐h period. Standard echo analysis software was used to detect fish traces and estimate the vertical and temporal distribution of fish abundance. Fish were sampled with a winter seine. 3. Prominent diel vertical migration in response to changing light level was detected throughout the study period (late winter to spring). Fish were highest in the water column at sunset and sunrise. In daylight, most detected fish were well below 10‐m depth. The number of fish detected was greatest during the night when they occurred throughout almost the whole water column, sometimes with a considerable number very close to the ice. Fish were mostly vendace and whitefish. 4. It became evident from data from the up‐beaming transducer that at night fish may occupy the layer closest to the surface. These fish would not have been detected if we had only used the down‐beaming transducer. The overall pattern of DVM in winter was very similar to that in summer. The results support the suggestion that DVM is a genetically fixed behavioural trait responding to the contemporary level of illumination.     

The proangiogenic factor ephrin-A1 is up-regulated in radioresistant murine tumor by irradiation

While the pre-treatment status of cancer is generally correlated with outcome, little is known about microenvironmental change caused by anti-cancer treatment and how it may affect outcome. For example, treatment may lead to induction of gene expression that promotes resistance to therapy. In the present study, we attempted to find a gene that was both induced by irradiation and associated with radioresistance in tumors. Using single-color oligo-microarrays, we analyzed the gene expression profiles of two murine squamous cell carcinomas, NR-S1, which is highly radioresistant, and SCCVII, which is radiosensitive, after irradiation with 137-Cs gamma rays or carbon ions. Candidate genes were those differentially regulated between NR-S1 and SCCVII after any kind of irradiation. Four genes, Efna1 (Ephrin-A1), Sprr1a (small proline-rich protein 1A), Srgap3 (SLIT-ROBO Rho GTPase activating protein 3) and Xrra1 [RIKEN 2 days neonate thymus thymic cells (NOD) cDNA clone E430023D08 3'], were selected as candidate genes associated with radiotherapy-induced radioresistance. We focused on Efna1, which encodes a ligand for the Eph receptor tyrosine kinase known to be involved in the vascular endothelial growth factor (VEGF) pathway. We used immunohistochemical methods to detect expression of Ephrin-A1, VEGF, and the microvascular marker CD31 in radioresistant NR-S1 tumor cells. Ephrin-A1 was detected in the cytoplasm of NR-S1 tumor cells after irradiation, but not in SCCVII tumor cells. Irradiation of NR-S1 tumor cells also led to significant increases in microvascular density, and up-regulation of VEGF expression. Our results suggest that radiotherapy-induced changes in gene expression related with angiogenesis might also modulate microenvironment and influence responsiveness of tumors.