Differential modulation of signaling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228

(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone (FR901228), a natural anticancer depsipeptide, induces apoptosis of ras-transformed 10T1/2 cells whereas it induces growth arrest of nontransformed counterpart cells in G0/G1 phase of the cell cycle. Our study of the effect of FR901228 treatment on intracellular signaling pathways reveals a discriminating activity of FR901228 to regulate signaling cascades differently in ras-transformed 10T1/2 cells and nontransformed counterpart cells. Induction of apoptosis of ras-transformed cells by FR901228 correlates with suppression of the extracellular signal-regulated kinase (ERK) signaling pathway through reduction of Raf expression and deactivation of Mek and Erk, inhibition of the phosphoinositide-3 kinase (PI3-K) pathway indexed by suppression of Akt activity, suppression of p38 activity, and activation of caspase-3. Expression of p21(Cip1) is not induced in ras-transformed cultures undergoing apoptosis induced by FR901228. In contrast, FR901228 induces p21(Cip1) expression in nontransformed counterpart cultures growth-arrested in G0/G1 that is also accompanied by moderate induction of the kinase activities of Raf, Mek, Erk, and Akt, but not accompanied by activation of caspase-3 or changes in p38 activity. Our study indicates a potential value of FR901228 in the treatment of cancer cells involving aberrant regulation of Ras through preferential induction of the caspase cascade and suppression of the ERK, PI3-K, and p38 pathways.     

Celecoxib to decrease urinary retention associated with prostate brachytherapy

PURPOSE: To retrospectively evaluate the effect of celecoxib in preventing urinary retention following prostate brachytherapy. MATERIALS AND METHODS: Between December 1997 and November 2001, 149 patients underwent a prostate implant. Medical records were reviewed to identify those who had acute urinary retention after the procedure. Urinary retention was scored based on replacement of the urinary catheter and the number of calls to the clinic and/or unscheduled clinic visits within 1 month after the implant. RESULTS: The use of celecoxib was associated with a decreased need for replacement of the catheter (p=.04) and decreased number of calls to the clinic and/or unscheduled clinic visits (p=.002). No patient who was given celecoxib for 1 week before brachytherapy required a urinary catheter compared to 14 (of 120) who did not receive celecoxib. CONCLUSIONS: The use of celecoxib appears to result in decreased urinary retention following prostate brachytherapy.     

Partial breast brachytherapy after lumpectomy: low-dose-rate and high-dose-rate experience

PURPOSE: The use of partial breast brachytherapy (PBB) after lumpectomy for selected patients with early-stage breast cancer reduces the adjuvant radiotherapy treatment time to <1 week. Despite the advantages of accelerated treatment, maintaining an acceptable cosmetic outcome is important. In a cohort of patients who received low-dose-rate (LDR) or high-dose-rate (HDR) PBB after lumpectomy, the clinical characteristics and treatment parameters were analyzed to identify predictors for an unfavorable cosmetic outcome. METHODS AND MATERIALS: Early-stage breast cancer patients with clear resection margins and 0-3 positive lymph nodes were eligible for PBB. Uniform guidelines for target definition and brachytherapy catheter placement were applied. The HDR PBB dose was 34 Gy in 10 fractions within 5 days, and the LDR dose was 45 Gy given at a rate of 50 cGy/h. The end points included incidence of radiation recall reaction, telangiectasias, and cosmetic-altering fibrosis. RESULTS: Between 1995 and 2000, 44 patients with early-stage breast cancer received PBB without adjuvant external beam radiotherapy after lumpectomy (31 HDR PBB, 13 LDR PBB). After a median follow-up of 42 months (range 18-86), all patients remained locally controlled. The overall rate of good/excellent cosmetic outcome was 79.6% overall and 90% with HDR PBB. Radiation recall reactions occurred in 43% of patients (6 of 14) who received adriamycin. LDR PBB and adriamycin were significant predictors for late unfavorable cosmetic changes in univariate analysis (p = 0.003 and p = 0.005, respectively). CONCLUSION: Although a high rate of local control and good/excellent cosmetic outcome is provided with HDR PBB, the risk of unfavorable cosmetic changes when treated with both LDR PBB and adriamycin is noteworthy. This suggests that HDR PBB is preferred in patients for whom adriamycin is indicated.     

Use of the think-aloud method to identify factors influencing purchase of bread and cereals by low-income African American women and implications for whole-grain education

The think-aloud method was used to determine factors influencing bread and cereal purchase by low-income African American women that have implications for whole-grain education. Women (N=70) were audiotaped as they thought aloud while purchasing groceries. Because bread and cereal account for the majority of whole-grain products consumed, transcribed verbalizations regarding purchase of bread and cereals were analyzed using content analysis procedures. Cost, preferences, eating and buying habits, and nutrition were the most important factors that influenced purchase. Nutrition issues included a general desire to eat healthy foods and specific concerns about fat, calcium, and calories, but no mention of wanting to purchase whole-grain products. Whole-grain education should focus on identification of whole-grain products, health benefits, and low-cost and tasty whole-grain options for mothers and children.     

Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors

The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.     

Study of an outbreak of ciguatera fish poisoning in Hong Kong.

Ciguatera fish poisoning (CFP) has been a significant and increasing public health problem in Hong Kong since 1980s. With growing demand for imported live coral fishes, the number of people who suffered from this disease has also been increasing. An outbreak of CFP in 2004 was the second most prominent in record as compared with the most significant one that occurred in 1998. In 2004, out of a total of 823 reported food poisoning outbreaks involving 3159 persons, 65 incidents (7.9%) affecting 247 people (7.8%) were attributed to CFP. Validated mouse bioassay analysis of surveillance samples revealed that seven samples (13%) were confirmed to be contaminated with ciguatoxins (CTXs). Typical symptoms of CTXs were found in mice injected with 20mg of fish extracts. The causative fishes included Cheilinus undulatus, Epinephelus coioides, Plectropomus areolatus, and Plectropomus leopardus. Most of these CTX-positive samples analyzed had only trace amounts of CTXs in their extract, except a C. undulatus sample which contained a mice lethal dose (2.5MU/20mg ether extract). This fish species was also the major origin of coral fish that caused clusters of CFP in the last quarter of 2004. Cigua-Check analysis of 20 flesh grains from seven CTX-positive fishes, previously confirmed as CTX-positive samples by mouse bioassay, showed that 50% of flesh grains were CTX contaminated.     

Comparison of chemotherapy education and patient preferences in community versus academic gynecology oncology clinics.

PURPOSE: To evaluate and compare patients' preferences in receiving chemotherapy education from health care teams in community versus academic clinics. METHODS: Results from a 13-question questionnaire about the chemotherapy education preferences of patients in three community gynecology oncology clinics were compared to the results from a similar study previously conducted in an academic gynecology oncology clinic. RESULTS: A total of 57% of the 203 community-clinic respondents (116) and 67% of the 282 academic-institution respondents (189) who completed questionnaires had previously received chemotherapy. Of the patients treated in community clinics, almost 60% preferred chemotherapy education to be provided in written form and directly by a health care professional compared to 87% of the patients in academic clinics. Overall, 88% of the patients in the community clinics believed they received adequate information, compared to 63% of the patients in the academic setting. Patients in the community clinics wanted to get more in-depth answers to questions such as 'What is chemotherapy?' (54%) and 'How it is given?' (55%). In addition, community patients also wanted to know more about 'Why chemotherapy stops working?' (72%) and 'What to do and who to call about side effects?' (60%). In the academic setting, patients were less likely to want to know more about these chemotherapy related questions (42, 35, 57, and 49, respectively). CONCLUSIONS: Patients preferred to receive written chemotherapy education that was reviewed with a healthcare professional and that gave more detailed information about the chemotherapeutic drugs themselves and how to prevent and manage side effects. As a result of this questionnaire, the patient education materials used at our institution will be revised to better address patients' preferences in both treatment settings.     

Racial/ethnic minority segregation and low birth weight: a comparative study of Chicago and Toronto community-level indicators

We examined the association between racial/ethnic minority segregation and low birth weight (LBW) in Chicago and Toronto communities. While previous work has documented the importance of contextual effects on LBW, these studies have usually been conducted within a single city. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW in Chicago (N = 77 communities) and Toronto (N = 140 communities). Results indicate that racial/ethnic minority segregation, unemployment, and low educational attainment are not associated with LBW in Toronto, while these indicators have strong and significant associations with LBW in Chicago. In a combined model with data from both cities, a 10% increase in minority composition is associated with a 0.5% increase in LBW, controlling for the effects of unemployment and low educational attainment. Stratified models show that this effect is only significant in Chicago, and subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Future research should consider additional cities for comparative analysis. Such work could test the notion that Chicago and Toronto represent opposite sides of a spectrum, reflecting variability in how social determinants map on to public health outcomes. Future research should also examine the significant heterogeneity observed in highly segregated communities, particularly in Chicago.     

Applying the theory of planned behavior to promotion of whole-grain foods by dietitians

The objective of this preliminary study was to apply the theory of planned behavior to explain dietitians’ intentions to promote whole-grain foods. Surveys were mailed to a random national sample of registered dietitians to assess knowledge and attitudinal, normative, and control beliefs regarding intention to promote whole-grain foods, with a 39% return rate (n=776, with 628 usable surveys from those working in direct patient care). About half of the respondents had a master’s degree, and 58% had substantial experience in the dietetics field. The theory of planned behavior explained intention to promote whole grains to a moderate extent (df=3, F=74.5, R²=0.278, P<.001). Most were positive about the health benefits, and few perceived barriers to promotion. However, many had low levels of knowledge and self-efficacy regarding ability to help clients consume more whole-grain foods. Continuing education for dietitians should use strategies that enhance self-efficacy regarding ability to promote whole-grain foods.