p53 genetic abnormalities and P-glycoprotein expression in stump and primary gastric carcinomas

BACKGROUND/AIMS: Genetic abnormalities of the p53 gene may play a major role in the carcinogenesis of gastric stump carcinomas (GSC) and intestinal-type primary gastric carcinomas (IPGC). Also, they may modulate P-gp expression producing chemoresistance. The aim of this article is to analyze p53 genetic abnormalities and the influence of p53 gene status on P-gp expression in both types of carcinomas. METHODOLOGY: Forty-two paraffin-embedded samples of gastric carcinomas corresponding to 17 GSC and 25 IPGC were studied. P53 genetic abnormalities in exon 5-9 were screened by direct sequencing of PCR products. P53 and P-glycoprotein (P-gp) were assessed by a standard streptavidin-biotin immunoperoxidase method. Anti-p53 DO7 and anti-P-gp C494 were used as primary antibodies. RESULTS: Fourteen p53 mutations were found, 5 in GSC (29%) and 9 in IPGC (36%). Thirteen mutations were base-pair substitutions that produced a change in the amino acid sequence. Eight mutations were located at exon 7 (57%). P53 nuclear immunopositivity was observed in 12 GSC (71%) and 15 IPGC (60%). Only two carcinomas (1 IPGC and 1 GSC) harboring a p53 mutation did not show any p53 expression. All except one of the gastric carcinomas having a p53 mutation showed medium or high P-gp expression. However, there was no difference in P-gp expression between tumors with and without p53 mutation. CONCLUSIONS: The p53 genetic alterations found in GSC and IPGC could originate from a similar pathogenetic pathway. No association was demonstrated between p53 gene status and P-gp expression, although most of the carcinomas harboring a p53 mutation showed medium or high P-gp expression.     

Methodology of a diabetes prevention translational research project utilizing a community-academic partnership for implementation in an underserved Latino community

Background  

Latinos comprise the largest racial/ethnic group in the United States and have 2–3 times the prevalence of type 2 diabetes mellitus as Caucasians.     

What patients value when oncologists give news of cancer recurrence: commentary on specific moments in audio-recorded conversations

Purpose.

Recommendations for communicating bad or serious news are based on limited evidence. This study was designed to understand patient perspectives on what patients value when oncologists communicate news of cancer recurrence.

Study Design and Methods.

Participants were 23 patients treated for a gastrointestinal cancer at a tertiary U.S. cancer center within the past 2 years, who had semistructured qualitative interviews in which they listened to audio recordings of an oncology fellow discussing news of cancer recurrence with a standardized patient. Participants paused the audio recording to comment on what they liked or disliked about the oncologist''s communication.

Results.

Three themes were identified that refine existing approaches to discussing serious news. The first theme, recognition, described how the oncologist responded to the gravity of the news of cancer recurrence for the patient. Participants saw the need for recognition throughout the encounter and not just after the news was given. The second theme, guiding, describes what participants wanted after hearing the news, which was for the oncologist to draw on her biomedical expertise to frame the news and plan next steps. The third theme, responsiveness, referred to the oncologist''s ability to sense the need for recognition or guidance and to move fluidly between them.

Conclusion.

This study suggests that oncologists giving news of cancer recurrence could think of the communication as going back and forth between recognition and guidance and could ask themselves: “Have I demonstrated that I recognize the patient''s experience hearing the news?” and “Have I provided guidance to the next steps?”     

The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.

PURPOSE: It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain. EXPERIMENTAL DESIGN: We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method. RESULTS: The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance. CONCLUSIONS: These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.     

National Trends in Smoking Behaviors Among Mexican,Puerto Rican,and Cuban Men and Women in the United States

Objectives. We examined trends in smoking behaviors across 2 periods among Mexicans, Puerto Ricans, and Cubans in the United States.Methods. We analyzed data from the 1992–2007 Tobacco Use Supplements to the Current Population Survey. We constructed 2 data sets (1990s vs 2000s) to compare smoking behaviors between the 2 periods.Results. Significant decreases in ever, current, and heavy smoking were accompanied by increases in light and intermittent smoking across periods for all Latino groups, although current smoking rates among Puerto Rican women did not decline. Adjusted logistic regression models revealed that in the 2000s, younger Mexicans and those interviewed in English were more likely to be light and intermittent smokers. Mexican and Cuban light and intermittent smokers were less likely to be advised by healthcare professionals to quit smoking. Mexicans and Puerto Ricans who were unemployed and Mexicans who worked outdoors were more likely to be heavy smokers.Conclusions. Increases in light and intermittent smoking among Mexican, Puerto Rican, and Cuban Americans suggest that targeted efforts to further reduce smoking among Latinos may benefit by focusing on such smokers.Since 2000, Latinos have experienced the largest population growth of all US racial/ethnic groups, making Latinos the largest ethnic minority group in the country at 16.3% of the population.1 Mexicans, Puerto Ricans, and Cubans are the 3 largest Latino national and family background groups in the United States.1 The leading causes of death among Latinos are coronary heart disease and cancer, both of which are strongly associated with tobacco use.2,3 Although differences in smoking rates by Latino national origin groups have been found,4–6 very little research has examined trends in smoking behaviors for various Latino national origin groups by gender in the United States.The aggregation of smoking rates for various Latino national origin groups masks important variations within the population group.4 For example, smoking prevalence rates as determined by national data from 2008 are highest among Cubans (21.5%), followed by Mexicans (20.1%), and Puerto Ricans (18.6%).3 Puerto Ricans and Cubans are also more likely to be current smokers than are Mexicans.7 Furthermore, although research grounded on a nationally representative sample found that Latinos were approximately 4.5 times more likely to be light smokers than were non-Hispanic Whites,8 that study provided only aggregated rates for all Latinos and did not differentiate between national origin groups. Gender differences have also been reported among disaggregated Latino groups. A higher prevalence of smoking has been reported among Mexican (25.0%), Puerto Rican (27.6%), and Cuban (24.7%) men than among Mexican (10.4%), Puerto Rican (24.2%), and Cuban (12.4%) women.7 The lower rates of smoking among women have been consistent in surveys of Latinos.5,7,9 Results from these studies, although informative, have generally been determined by aggregated Latino data or data from a single survey time point. Although such data are valuable and can demonstrate existing gender differences, national-level trends from Latino nationality groups in the United States add valuable information that have not been previously reported.Previous research has also identified social and environmental factors associated with Latinos’ smoking behaviors. Acculturation to mainstream US culture plays a significant role in one’s health behaviors,10 and as Latinos acculturate, their smoking behaviors become similar to those of non-Hispanic Whites.7 Existing research has also revealed that Latinos are less likely to quit smoking,11 receive tobacco screening, and be advised to quit by a physician than are non-Hispanic Whites.12–15 A health professionals’ advice to quit smoking has been found to increase the likelihood that a smoker will successfully quit.16,17 Lastly, workplace smoking policies have also influenced smoking prevalence and intensity.18–20 Work environments adopting a smoke-free policy saw a 14% decrease in individuals’ smoking.21 When examining national-level smoking behaviors among Latinos, it is important to account for social and environmental factors such as acculturation, physician advice to quit smoking, and work environment smoking policies, as they may influence smoking behaviors.Existing research on smoking behaviors among Latino national origin groups has been predicated on data from specific regions of the United States.4,22–25 Although regional data are important for the development of community-level interventions,4 national-level data provide an overview of the country’s progress in tobacco control as well as remaining and emerging challenges for Latinos nationwide. We compared smoking behaviors across 2 periods, about a decade apart, among Mexicans, Puerto Ricans, and Cubans. Our goals in these analyses were (1) to compare Latino national origin groups across 2 periods to examine factors affecting changes in smoking behavior within and between groups, and (2) to evaluate demographic factors that influence current smoking behaviors within Latino national origin groups in the most recent period available. Examining long-term national trends in Latino smoking behaviors may prove vital to policymakers, public health officials, community workers, and interventionists as they address tobacco-related issues.     

Melatonin concentration in the umbilical artery and vein in human preterm and term neonates and neonates with acute fetal distress

In order to assess the existence of a rhythmic secretion of melatonin (aMT) in newborns and whether this rhythm is affected by neonatal stress, we studied 112 newborns classified in three groups: normal babies delivered at term, preterm infants born before the 38th week, and babies with fetal distress. Melatonin was measured by RIA in the umbilical artery and vein at the time of birth. Melatonin levels in umbilical arterial and venous blood showed a diurnal rhythm in all groups. Melatonin levels in umbilical cord artery and vein were closely related. Nocturnal melatonin levels were increased in newborns with acute fetal distress in comparison with normal term and preterm neonates. These results suggest that (1) a rhythm of aMT secretion exists in newborns, although it cannot be determined whether this rhythm is of maternal or fetal origin and (2) neonatal stress (acute fetal distress) increases aMT production during the night in comparison with normal term and preterm neonates.     

Lipoprotein profile in elderly persons from northwestern Spain consuming the Atlantic diet, a variant of the Mediterranean diet

To screen some cardiovascular risk factors in institutionalized elderly persons of the Spanish Northwest who consume the Atlantic variant of the Mediterranean diet, rich in vegetables, fruit, meat, fish, olive oil and dairy products, anthropometric and dietary measurements were carried out and serum glucose and lipoprotein values were determined in 94 subjects. Men consumed significantly more legumes, fruit, meat, alcohol and precooked foods but fewer vegetables than women. Significant positive correlations were found between total fat and MUFA consumption and HDL-cholesterol. Fish intake correlated negatively with total cholesterol (TC) and LDL-cholesterol. The prevalence of high TC, LDL-cholesterol, triglyceride and TC/HDL-cholesterol levels was 29%, 37%, 21%, 25% respectively, and that of low HDL-cholesterol was 15%. Women displayed a higher prevalence of dyslipemia, with significantly higher TC and higher LDL-cholesterol levels than men. Fifty percent of the women aged 75-80 presented concurrent hyperglycemia, excess weight and hypertriglyceridemia, predisposing them to the metabolic syndrome. Nonetheless, as regards the lipoprotein profile, the Atlantic diet appears appropriate for most institutionalized elderly persons.     

Effect of a low-tryptophan diet as an adjuvant to conventional neuroleptic therapy in schizophrenia.

Eleven patients with DSM-III-R schizophrenia were entered into a 4-day tryptophan (TRP)-deficient diet. The diet lowered total plasma TRP levels in all patients; during the diet phase, there was a greater than 50% reduction in mean total plasma TRP levels from the pre-diet phase. The low-TRP diet improved performance on the Stroop Color and Word Test. These data are especially intriguing in view of the suggestion that a deficit in color-word naming is related to frontal lobe dysfunction and the possible occurrence of frontal lobe abnormalities in patients with schizophrenia. Interestingly, depressive symptomatology did not emerge on the TRP-deficient diet, despite the lowering of total plasma TRP levels. There were statistically significant improvements noted on objective ratings of the severity of psychotic symptomatology; however, these statistical improvements were without obvious clinical significance, as the magnitude of the changes on the behavioral ratings were minimal. The results of this study suggest that there might be some adjuvant potential for a low-TRP diet in the treatment of schizophrenia, and that schizophrenia or antipsychotic medications might offer some protection against the depressive effects of a TRP-deficient diet.