All-trans-retinoic acid (ATRA) induces growth inhibition, differentiation, and apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL, expression of promyelocytic leukemia protein retinoic acid receptor-␣ (PML-RAR␣) fusion protein, owing to the t(15; 17) reciprocal translocation, leads to a block in the promyelocytic stage of differentiation. Here, we studied molecular mechanisms involved in ATRA-induced growth inhibition and myeloid cell differentiation in APL. By employing comprehensive high-throughput proteomic methods of 2-dimensional (2-D) gel electrophoresis and amino acid-coded mass tagging coupled with electrospray ionization (ESI) mass spectrometry, we systematically identified a total of 59 differentially expressed proteins that were consistently modulated in response to ATRA treatment. The data revealed significant downregulation of eukaryotic initiation and elongation factors, initiation factor 2 (IF2), eukaryotic initiation factor 4AI (eIF4AI), eIF4G, eIF5, eIF6, eukaryotic elongation factor 1A-1 (eEF1A-1), EF-1-␦, eEF1␥, 14-3-3⑀, and 14-3-3/␦ (P < .05). The translational inhibitor DAP5/p97/NAT1 (deathassociated protein 5) and PML isoform-1 were found to be up-regulated (P < .05). Additionally, the down-regulation of heterogeneous nuclear ribonucleoproteins (hnRNPs) C1/C2, UP2, K, and F; small nuclear RNPs (snRNPs) D3 and E; nucleoprotein tumor potentiating region (TPR); and protein phosphatase 2A (PP2A) were found (P < .05); these were found to function in pre-mRNA processing, splicing, and export events. Importantly, these pro-

Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. We investigated the role and the regulation of PDCD4 in the terminal differentiation of acute myeloid leukemia (AML) cells. Expression of PDCD4 was markedly up-regulated during all-trans retinoic acid (ATRA) -induced granulocytic differentiation in NB4 and HL60 AML cell lines and in primary human promyelocytic leukemia (AML-M3) and CD34 + hematopoietic progenitor cells but not in differentiation-resistant NB4.R1 and HL60R cells. Induction of PDCD4 expression was associated with nuclear translocation of PDCD4 in NB4 cells undergoing granulocytic differentiation but not in NB4.R1 cells. Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells. In contrast, PDCD4 was not up-regulated during monocytic/macrophagic differentiation induced by 1,25-dihydroxyvitamin D3 or 12-O-tetradecanoyl-phorbol-13-acetate in NB4 cells or by ATRA in THP1 myelomonoblastic cells. Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27Kip1 and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21 Waf1/Cip1 , and tissue transglutaminase (TG2).

Objective This study evaluated the effect of two home-based exercise interventions (one culturally-adapted and one standard) on changes in Social Cognitive Theory (SCT) variables, physical activity (PA) and sedentary time (ST), and to determine the association between changes in SCT variables and changes in PA and ST in Hispanic breast cancer survivors. Method Project VIVA! was a 16-week randomized controlled pilot study to test the effectiveness and feasibility of a culturally-adapted exercise intervention for Mexican American and Puerto Rican breast cancer survivors in Houston, Texas and San Juan, Puerto Rico, respectively. Women (N=89) completed questionnaires on SCT variables, PA and ST and were then randomized to a 16-week culturally-adapted exercise program, a non-culturally adapted standard exercise intervention or a wait-list control group. Multiple regression models were used to determine associations between changes in SCT variables and changes in PA and ST. Results Participants were in their late 50s (58.5 ± 9.2 years) and obese (31.0 ± 6.5 kg/m2). Women reported doing roughly 34.5 minutes/day of PA and spending over 11 hours/day in sedentary activities. Across groups, women reported significant increases in exercise self-efficacy and moderate-intensity, vigorous-intensity, and total physical activity from baseline to follow-up (p<.05). Increased social support from family was associated with increases in vigorous-intensity PA. Increases in social modeling were associated with increases in moderate-intensity and total PA and decreases in ST from baseline to follow-up (p<.05). Conclusions Hispanic cancer survivors benefit from PA interventions that focus on increasing social support from family and friends and social modeling.

The present study aimed to investigate single-agent liposomal all-trans retinoic acid (Lipo-ATRA) in untreated acute promyelocytic leukemia (APL). Induction therapy consisted of Lipo-ATRA 90 mg/m2 i.v. every other day. Patients in complete remission (CR) continued to receive Lipo-ATRA 90 mg/m2 i.v. three times a week for 9 months. Idarubicin was added only if a polymerase chain reaction test for promyelocytic leukemia-retinoic acid receptor alpha (sensitivity level, 10(-4)), performed every 3 months from CR, was positive. The results were compared with those of a historical control group treated with oral ATRA and idarubicin. Lipo-ATRA induced CR in 79% of patients; CR rates were 92% and 38% in patients with white blood cell (WBC) counts <10 x 10(9)/L and >10 x 10(9)/L, respectively. Ten of the 26 responders to Lipo-ATRA remain in first CR at a median of 6.4 years, despite never receiving idarubicin; all 10 had initial WBC counts <10 x 10(9)/L. The 5-year survival rate was 76% for patients treated with Lipo-ATRA. Comparisons with oral ATRA+idarubicin as given at M. D. Anderson are confounded because of their historical nature and the absence of ATRA from post-remission therapy in the former group. Nonetheless, a multivariate Cox model identified higher WBC counts and older age, but not treatment (historical vs. Lipo-ATRA), as being predictive of shorter relapse-free and overall survival. Lipo-ATRA can cure patients presenting with WBC counts <10 x 10(9)/L (low risk) without additional therapy, contrary to conventional ATRA, which, when given alone, probably cures no patients. The observation that patients can be cured of APL without the use of chemotherapy should encourage further study of 'targeted' therapy in APL and in other leukemias.