Is the seasonal variation in cancer prognosis caused by sun-induced folate degradation?

Recently, we have documented that the season of diagnosis affects the prognosis of Hodgkin's lymphoma, colon-, breast- and prostate-cancer patients in Norway. The relative risk of death was lower for the patients diagnosed during summer and autumn when compared with the winter diagnosis. We here hypothesise that UV (ultraviolet) induced degradation of folate may be the reason for the observed seasonal variations in cancer prognosis. It is known that folic acid, a synthetic form of folate, is degraded by UV radiation. We have also found that the most common folate derivative in the human body, 5-methyltetrahydrofolate, is UV sensitive.     

Histological and mechanical evaluation of self-setting calcium phosphate cements in a sheep vertebral bone void model

We investigated the histological and compressive properties of three different calcium phosphate cements (CPCs) using a sheep vertebral bone void model. One of the CPCs contained barium sulfate to enhance its radiopacity. Bone voids were surgically created in the lumbar region of 23 ovine spines - L3, L4, and L5 (n = 69 total vertebral bodies) - and the voids were filled with one of the three CPCs. A fourth group consisted of whole intact vertebrae. Histologic evaluation was performed for 30 of the 69 vertebrae 2 or 4 months after surgery along with radiographic evaluation. Compressive testing was performed on 39 vertebrae 4 months after surgery along with micro-CT analysis. All three CPCs were biocompatible and extremely osteoconductive. Osteoclasts associated with adjacent bone formation suggest that each cement can undergo slow resorption and replacement by bone and bone marrow. Compressive testing did not reveal a significant difference in the ultimate strength, ultimate strain, and structural modulus, among the three CPCs and intact whole vertebrae. Micro-CT analysis revealed good osseointegration between all three CPCs and adjacent bone. The barium sulfate did not affect the CPCs biocompatibility or mechanical properties. These results suggest that CPC might be a good alternative to polymethylmethacrylate for selected indications.     

Acute-phase reactant proteins and complement components and inhibitors in patients with ovarian cancer

The levels of acute-phase reactant proteins, complement components and inhibitors were measured in sera of 15 patients with stage IV ovarian cancer. Marked elevations of the concentrations of the α-1-acid glycoprotein, α-1-antitrypsin, and haptoglobin, and of C3, C4, C3PA, and the inactivator of C3 (C3bINA) were found compared to the control sera. Laparotomy and tumor extirpation produced a temporary decrease of the level of all but α-proteins. Chemotherapy with Thiotepa brought about a decrease in serum level of acute-phase reactants and complement components and C3bINA, with a concomitant rise in total protein level. Measuring of acute-phase reactants and complement inhibitors may be an additional tool in evaluating the efficiency of chemotherapy in patients with advanced cancer of the ovary.     

Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer.

Five hundred and twenty seven colorectal carcinomas were reviewed histologically. A multivariate analysis (Cox) was used to test the prognostic importance of certain histological features (invasiveness, inflammatory reaction, and amount of fibrous tissue) at the tumour edge after allowance had been made for clinicopathological stage, tumour site, and histological type and grade. A poorly defined tumour border, lack of inflammatory reaction, and a pronounced fibrosis (desmoplasia) at the tumour edge were associated with unfavourable stage distributions, but each of these features also had an independent effect on prognosis.     

Toxic oxygen species in monocyte-mediated antibody-dependent cytotoxicity

The role of toxic oxygen species in monocyte-mediated ADCC against the myelogenous cell line K-562 was investigated. Freshly isolated human monocytes caused 40% specific lysis of antibody-coated K-562 cells (Ab-K-562). Monocytes challenged with Ab-K-562 gave a small but definite luminol-dependent chemiluminescence response, indicating that a respiratory burst with generation of toxic oxygen species had been elicited. Generation of hydrogen peroxide in areas of close apposition between the monocyte and the Ab-K-562 plasma membranes was demonstrated by electron microscopy using precipitation of cerium ions as a cytochemical stain for hydrogen peroxide. Catalase inhibited the formation of cerium precipitates in the interaction zone between monocytes and Ab-K-562 cells. Despite evidence that toxic oxygen species were generated, the monocytes' cytolytic activity against Ab-K-562 was not inhibited by superoxide dismutase, catalase, or azide. Enzymatically generated fluxes of superoxide anion or hydrogen peroxide were not cytolytic to K-562 cells but did have a cytostatic effect. We conclude that toxic oxygen species are generated when human monocytes are challenged with Ab-K-562. However, these toxic oxygen species do not appear to be the major mediators of the monocytes' cytolytic activity in this experimental system.     

Validation of a severity index in female urinary incontinence and its implementation in an epidemiological survey.

STUDY OBJECTIVE--The aim was to validate a simple severity index of female urinary incontinence for subsequent use in an epidemiological survey. DESIGN--The index was created by multiplying the reported frequency (four levels) by the amount of leakage (two levels). The resulting index value (1-8) was further categorised into slight (1-2), moderate (3-4), and severe (6-8). It was validated against a 48 hour "pad weighing" test. Thereafter, an anonymous postal questionnaire survey was performed and the index was used to assess the severity of the leakage. A question about the impact of incontinence was also included. SETTING--The outpatient clinic of the Department of Gynaecology and Obstetrics, Trondheim University Hospital and the rural community of Rissa, Norway. PARTICIPANTS--Altogether 116 incontinent women referred to the clinic by their GP and all 2366 adult women living in Rissa. RESULTS--The difference in median pad weights between moderate and slight incontinence was 9g/24h (95% confidence interval 0-27). The corresponding difference between severe and moderate incontinence was 17g/24h (95% CI 5-30). In the epidemiological survey 29.4% reported urinary incontinence (response rate 77%). The prevalence tended to be highest in middle life and old age. Forty six per cent were classified as slight, 27% moderate, and 27% severe. There was a strong correlation between severity and impact (R = 0.59, p < 0.001). CONCLUSION--The severity index may be a useful tool for assessing the severity of female urinary incontinence in epidemiological surveys. It is confirmed that urinary incontinence is very prevalent in adult women, but most should not be regarded as potential patients.     

Cardiac accumulation of bone marrow mononuclear progenitor cells after intracoronary or intravenous injection in pigs subjected to acute myocardial infarction with subsequent reperfusion.

OBJECTIVE: The purpose of the present study was to compare the efficacy of intracoronary and intravenous injection of autologous progenitor cells for homing to the acutely infarcted but reperfused myocardium in pigs. METHODS: Myocardial infarction was induced in 11 anesthetized pigs by 60-min balloon inflation in the mid LAD. After balloon deflation, reperfusion was verified and autologous CD31(+) progenitor cells, or bone marrow mononuclear cells, labeled with PKH67, were injected either intracoronarily (n=6) or intravenously (n=3). By autopsy, 4-5 days after induction of infarction, tissue from the heart and other organs was obtained for fluorescence microscopy. RESULTS: In the heart, PKH(+) cells were detected throughout the reperfused infarcted myocardium, and the number of PKH(+) cells was significantly higher after intracoronary than after intravenous injection (3.2+/-0.55 vs. 0.33+/-0.17 cells/high-power field/10(6) cells injected, P=.01). Few PKH(+) cells were detected in the spleen, lung, mesenteric lymph node, and bone marrow. In an additional animal with a coil placed in the mid LAD, progenitor cells were not detected in the infarcted myocardium or in the normal myocardium. CONCLUSION: Autologous mononuclear and CD31(+) cells from bone marrow accumulated in the infarcted myocardium when injected intracoronarily or intravenously after established reperfusion, and the accumulation of cells was significantly greater after intracoronary injection than after intravenous injection. Accumulation of PKH(+) cells did not appear in the normal myocardium or in the nonreperfused infarcted myocardium. PKH(+) cells were detected in spleen, lung, and bone marrow but to a lesser degree than in the infarcted myocardium.     

Expression and In Vitro Functions of the Ghrelin Axis in Endometrial Cancer

Ghrelin is a peptide hormone produced in the stomach and a range of other tissues, where it has endocrine, paracrine and autocrine roles in both normal and disease states. Ghrelin has been shown to be an important growth factor for a number of tumours, including prostate and breast cancers. In this study, we examined the expression of the ghrelin axis (ghrelin and its receptor, the growth hormone secretagogue receptor, GHSR) in endometrial cancer. Ghrelin is expressed in a range of endometrial cancer tissues, while its cognate receptor, GHSR1a, is expressed in a small subset of normal and cancer tissues. Low to moderately invasive endometrial cancer cell lines were examined by RT-PCR and immunoblotting, demonstrating that ghrelin axis mRNA and protein expression correlate with differentiation status of Ishikawa, HEC1B and KLE endometrial cancer cell lines. Moreover, treatment with ghrelin potently stimulated cell proliferation and inhibited cell death. Taken together, these data indicate that ghrelin promotes the progression of endometrial cancer cells in vitro, and may contribute to endometrial cancer pathogenesis and represent a novel treatment target.