Adjuvant Treatment of Colorectal Cancer: Towards Tumor-specific Immunotherapies

Colorectal cancer is one of the leading causes of cancer-related mortality. After a series of clinical trials, the adjuvant 5-FU based chemotherapy has established a definitive role in the management of stage III colon cancer. The precise role for chemotherapy in stage II disease remains under investigation and less toxic treatment modalities like active specific immunotherapy have emerged as potentially attractive alternatives. It is most likely that the adjuvant treatment of colon cancer will move towards more tumor-specific immunotherapies using antibody- or vaccination-based strategies. Phase II/III clinical trials investigating these different modalities in colorectal cancer are reviewed.     

Specificity of CD8+ T cells from subunit-vaccinated and infected H-2b mice recognizing the 38 kDa antigen of Mycobacterium tuberculosis

CD8+ T cells have been implicated in protective anti-tuberculous immune responses, but little is known about the identity of mycobacterial antigens recognized by CD8+ T cells. In this study we identified the Mycobacterium tuberculosis 38 kDa protein as a target for murine CD8+ cytotoxic T lymphocytes (CTL) which were induced by vaccination of C57BL/6 mice with DNA delivered with a plasmid, with transfected tumour cells or by infection with tubercle bacilli. Using overlapping synthetic peptides covering the whole protein sequence, peptides predicted to contain H-2Kb or H-2Db motifs, as well as naturally processed peptides, we were able to identify CTL epitopes. Differences were demonstrated in peptide specificity between CTL from immunized or M. tuberculosis-infected mice. The identified CTL epitopes could be important for future analysis of the involvement of CD8+ T cells in M. tuberculosis infections and for vaccine development.      

Q-T prolongation and torsades de pointes in a patient with subarachnoid hemorrhage

An extreme Q-T prolongation in a patient with subarachnoid hemorrhage was observed. Multiple torsades de pointes occurred. Lidocaine, metoprolol, and atropine were not effective in controlling the arrhythmia, whereas shortening the Q-T interval by intravenous administration of orciprenaline or overdrive ventricular pacing was successful. The occurrence of T wave alternations was a sign of increased sympathetic activity.     

Regulation of heme synthesis in erythroid cells: hemin inhibits transferrin iron utilization but not protoporphyrin synthesis

The inhibition of delta-aminolevulinic acid (ALA) synthase activity by heme is commonly thought to regulate the overall rate of heme synthesis in erythroid cells. However, since heme inhibits erythroid cell uptake of iron from transferrin, we have tested the hypothesis that in reticulocytes heme regulates its own synthesis by controlling the cellular acquisition of iron from transferrin rather than by controlling the synthesis of ALA. We found that hemin added to reticulocytes in vitro inhibits not only the total cell incorporation of 59Fe from transferrin but also the incorporation of [2-14C]-glycine and transferrin-bound 59Fe into heme. However, hemin did not inhibit [2- 14C]-glycine incorporation into protoporphyrin. Furthermore, cycloheximide, which increases the level of non-hemoglobin heme in reticulocytes, also inhibited [2-14C]-glycine into heme but not into protoporphyrin. With high concentrations of ferric pyridoxal benzoylhydrazone (Fe-PBH), which, independent of transferrin and transferrin receptors, can be used as a source of iron for heme synthesis in reticulocytes, significantly more iron is incorporated into heme than from saturating concentrations of Fe-transferrin. This suggests that some step (or steps) in the pathway of iron from extracellular transferrin to protoporphyrin limits the overall rate of heme synthesis in reticulocytes. In addition, hemin in concentrations that inhibit the utilization of transferrin-bound iron for heme synthesis has no effect on the incorporation of iron from Fe-PBH into heme. Our results indicate that in reticulocytes heme inhibits and controls the utilization of iron from transferrin but has no effect on the enzymes of porphyrin biosynthesis and ferrochelatase. This mode of regulation of heme synthesis may be a specific characteristic of the hemoglobin biosynthetic pathway.     

Disparities in mammographic screening for Asian women in California: a cross-sectional analysis to identify meaningful groups for targeted intervention

Background  

Breast cancer is the most commonly diagnosed cancer among the rapidly growing population of Asian Americans; it is also the most common cause of cancer mortality among Filipinas. Asian women continue to have lower rates of mammographic screening than women of most other racial/ethnic groups. While prior studies have described the effects of sociodemographic and other characteristics of women on non-adherence to screening guidelines, they have not identified the distinct segments of the population who remain at highest risk of not being screened.