Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study

BACKGROUND: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results. OBJECTIVE: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults. DESIGN: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005. RESULTS: During a mean 7.2-y follow-up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32, 0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30, 0.83; P for trend = 0.03) for alpha-carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for beta-carotene. No significant associations were found for beta-cryptoxanthin, lutein and zeaxanthin, or lycopene intake. CONCLUSION: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer.     

Iodine prophylaxis—the protective factor against stomach cancer in iodine deficient areas

BACKGROUND: Poland has one of the highest death rates for stomach cancer in Europe. Moderate iodine deficiency and in consequence high goitre prevalence led to the implementation in 1996 of a very efficient mandatory model of iodine prophylaxis, based on household salt iodisation (30 +/- 10 mg KI/1 kg of salt). AIM OF THE STUDY: The aim of the study was evaluation of incidence rate of stomach cancer and its possible relation to increased iodine consumption in the years 1992-2004. METHODS: Iodine supply and effectiveness of iodine prophylaxis were evaluated on the basis of comparative analysis of goitre prevalence and ioduria in schoolchildren. To allow comparison between time periods with varying population age structures, the incidence rates of stomach cancer were standardized for age, using the "world standard population". The direct standardization method has been applied. For each sex, the time-trend of incidence rates was shown in graphs over the years 1991-2004. RESULTS: Evident increase in iodine consumption in this period of time was proved by rise in percentage of schoolchildren (6-8 years old) with ioduria above 100 microg/l from 11.4% in 1992-1993 to 52.9.1% in 2003. It was correlated with the decrease in goitre prevalence from 18.8% to 3.2% respectively. The 24-h thyroid uptake of (131)I in investigated population fell from 45.5% in 1986 to 26.8% in 1998. In Krakow the standardized incidence ratio of stomach cancer for men decreased from 19.1 per 100,000 to 15.7 per 100,000, and for women from 8.3 per 100,000 to 5.9 per 100,000 in the years 1992-2004. A significant decline of average rate of decrease was observed in men and women (2.3% and 4.0% per year respectively). CONCLUSION: Observed association between improved iodine supply and decrease of incidence of stomach cancer could indicate the protective role against stomach cancer of iodine prophylaxis in iodine deficient areas--further studies are necessary.     

Dosimetric study to assess the feasibility of intraoperative radiotherapy with electrons (ELIOT) as partial breast irradiation for patients with cardiac implantable electronic device (CIED)

Purpose

To report in-vivo dosimetry in the infraclavicular region, a potential site of a cardiac implantable electronic device (CIED) and to evaluate the absorbed dose from intraoperative radiotherapy with electrons (ELIOT).

Methods

27 non-cardiopathic breast cancer (BC) patients without CIED received quadrantectomy and ELIOT as partial breast irradiation. Before delivering ELIOT, two catheters, each containing eight thermoluminescent dosimeters (TLDs), were positioned in the infraclavicular region. TLDs internal catheter was located deep in the tumor bed while the external catheter was placed on patient’s skin.

Results

Data were available for 24/27 patients. The absorbed doses were referred to the dose of 21 Gy. Values measured by the external catheter were low, although statistically significant higher doses were found close to the applicator (mean values 0.26–0.49 Gy). External TLD doses in proximity of the applicator were lower than those detected by their internal counterparts. Values measured by the internal catheter TLDs varied according to the distance from the applicator while no correlation with tumor site and beam energy was found. The distance from the applicator to deliver <?2 Gy to a CIED was 2 cm, while from 2.5 cm the dose measured in all the patients became negligible.

Conclusions

This dosimetric study provided data to support the clinical use of ELIOT in BC patients having CIEDs as long as the suggested minimum safe distance of 2.5 cm is taken from the RT field in case of ELIOT single dose of 21 Gy, in the energy range of 6–10 MeV.

     

Comparative evaluation of simple indices using a single fasting blood sample to estimate beta cell function after islet transplantation

Six single fasting blood sample–based indices—Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2‐B%, C‐peptide/glucose ratio (CP/G), C‐peptide/glucose creatinine ratio (CP/GCr), and BETA‐2 score—were compared against commonly used 90‐minute mixed meal tolerance test (MMTT) serum glucose and beta score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx). We also tested whether the indices could identify the success of ITx based on the Igls classification of beta cell graft function. We analyzed values from 47 MMTT tests in 4 patients with up to 140 months follow‐up and from 54 MMTT tests in 13 patients with up to 42 months follow‐up. SUITO, CP/G, HOMA2‐B%, and BETA‐2 correlated well with the 90‐minute glucose of the MMTT and beta‐score (r 0.54‐0.76), whereas CP/GCr showed a modest performance (r 0.41‐0.52) while TEF showed little correlation. BETA‐2 and SUITO were the best identifiers and predictors of the need for insulin support, glucose intolerance, and ITx success (P < .001), while HOMA2‐B% and TEF were unreliable. Single fasting blood sample SUITO and BETA‐2 scores are very practical alternative tools that allow for frequent assessments of graft function.

     

Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia

BACKGROUND AND OBJECTIVES: A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology. We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein. DESIGN AND METHODS: A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis. Fluorescence in situ hybridization (FISH) and Southern blotting were used for mapping the translocation breakpoint and Western blotting for assessing protein expression. RESULTS: Immunophenotyping showed the presence of a B-cell population with strong expression of FMC7, CD22, CD79b, CD5 and k restricted surface immunoglobulins. Based on morphology and immunophenotypic markers the diagnosis of B-cell non-Hodgkin's lymphoma was made. Karyotyping revealed a clone with t(2;7)(p12;q21-22). Evidence for clonal evolution with additional abnormalities including a deletion of the TP53 was present. We established by FISH and Southern blotting that the breakpoint on 7q21-22 fell in a region 66kb telomeric to the previously reported breakpoint for the t(2;7) and was the same as that observed in a t(7;21). CDK6 protein was over-expressed. The patient received alkylating agents and splenectomy and is alive but the lymphocytosis persists with evidence of disease progression. INTERPRETATIONS AND CONCLUSIONS: We have demonstrated that CDK6 expression is dysregulated even when the breakpoint on 7q21-22 is located 66kb upstream from the coding region. Interestingly, the precise assignment of the lymphoma type in our case was not possible even when the splenic histology was analyzed.     

Recombinant Human Erythropoietin Treatment of Chronic Renal Failure Patients Normalizes Altered Phenotype and Proliferation of CD4‐positive T Lymphocytes

Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4⁺ T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4⁺ lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4⁺ T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4⁺CD95⁺, CD4⁺HLA‐DR⁺ cells, and lower percentages of CD4⁺CD69⁺ and CD4⁺CD28⁺ cells were observed in both rhEPO‐treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4⁺CD28⁺ and CD4⁺HLA‐DR⁺ subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPOβ. CD4⁺ lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO‐treated patients was similar to that observed in healthy controls. Fewer CD4⁺CD28⁺ T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0→G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4⁺ T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.     

Involvement of insula and cingulate cortices in control and suppression of natural urges

The physiology of control and suppression of natural urges isnot well understood. We used [¹⁵O]H₂O positron-emission tomographyimaging to identify neural circuits involved in suppressionof spontaneous blinking as a model of normal urges. Suppressionof blinking was associated with prominent activation of bilateralinsular-claustrum regions, right more than left; activationwas also found in bilateral anterior cingulate cortex (ACC),supplementary motor areas, and the face area of the primarymotor cortex bilaterally. These results suggest a central rolefor the insula possibly together with ACC in suppression ofblinking.