Patients who are obese make up a substantial proportion of individuals with cancer and may not benefit equitably from treatment. The impact of obesity on the efficacy of common cancer treatments is reviewed, and considerations are discussed for future studies that may contribute to the evidence base for the clinical care of this growing population.

Understanding mechanisms controlling expression of the ␣-spectrin gene is important for understanding erythropoiesis, membrane biogenesis, and spectrinlinked hemolytic anemia. We showed previously that a minimal ␣-spectrin promoter directed low levels of expression only in early erythroid development, indicating elements outside the promoter are required for expression in adult erythrocytes. Addition of noncoding exon 1 and intron 1 conferred a 10-fold increase in activity in reporter gene assays. In this report, we used a transgenic mouse model to show that addition of exon 1 and intron 1 to the ␣-spectrin promoter conferred tissue-specific expression of a linked A ␥-globin gene in erythroid cells at all developmental stages. Expression was nearly position-independent, as 21 of 23 lines expressed the transgene, and ␥-globin protein was present in 100% of erythrocytes, indicating uniform expression. Additional in vivo studies revealed that exon 1 functions as an insulator with barrier-element activity. Chromatin immunoprecipitation assays demonstrated that this region was occupied by the upstream stimulatory factors 1/2 (USF1/USF2), similar to the well-characterized chicken HS4 insulator. These data identify the first barrier element described in an erythrocyte membrane protein gene and indicate that exon 1 and intron 1 are excellent candidate regions for mutations in patients with spectrin-linked hemolytic anemia. (Blood. 2009;113:1547-1554) IntroductionSpectrin is the major structural component of the erythrocyte membrane skeleton that maintains cellular shape, regulates the lateral mobility of integral membrane proteins, and provides structural support for the lipid bilayer. 1 It is composed of 2 subunits, ␣-and ␤-spectrin, encoded by separate genes. 1,2 Throughout erythropoiesis, there are significant changes in the synthesis, expression, and membrane assembly of spectrin. Early in erythropoiesis, ␣-spectrin is synthesized in great excess, 3,4 a process controlled at the transcriptional level. 3,5,6 The molecular mechanisms that regulate the erythroid tissue-specific and developmental stage-specific expression of ␣-spectrin, including the mechanisms that control the increase in ␣-spectrin gene transcription to high levels during the early stages of erythropoiesis, are unknown.In the mature erythrocyte, quantitative and qualitative disorders of ␣-spectrin have been associated with inherited hemolytic anemias, including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). [7][8][9][10][11][12] In most recessive HSp and many HPP patients, there is a defect in ␣-spectrin mRNA accumulation associated with spectrin deficiency. 7,13,14 With a few rare exceptions, the cause of the defect in ␣-spectrin expression in erythrocytes of these patients is unknown, even after nucleotide sequence analysis of the exons corresponding to the ␣-spectrin coding region and the minimal promoter region. 15,16 Our previous studies demonstrated that a minimal ␣-spectrin promoter dire...

No abstract

Background We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post‐radiation therapy (RT), and now report ALND's long‐term impact at 1 year. Methods Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post‐RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. Results A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post‐RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). Conclusions In the setting of whole breast RT, our findings suggest that ALND has long‐term repercussions on breast skin thickening.