Race/Ethnicity-Based Concerns Over Understanding Cancer Diagnosis and Treatment Plan

BackgroundRace/ethnicity and culture influence illness perceptions, health beliefs and behaviors, and communication with health care providers. However, information about the impact of race/ethnicity on the understanding of cancer diagnosis and treatment plan is limited.MethodsNine hundred seventy-three cancer patients completed an information needs-assessment questionnaire prior to starting treatment at 20 geographically distinct clinical cancer sites within the University of Rochester Community Clinical Oncology Program network, x²Test was used to examine the association between race/ethnicity and education, occupation, and perception and use of available information. 7 test and analysis of covariance were used to examine race/ethnicity-based differences in concerns over understanding cancer diagnosis/treatment plan and the effect of race/ethnicity controlling for demographics.ResultsThere were 904 non-Hispanic white and 69 nonwhite (blacks, Latinos, and others) patients in the sample. Whites and nonwhites were comparable in educational attainment and occupation. However, there was a statistically significant race/ethnicity-based difference in concerns over understanding the diagnosis and treatment plan for cancer, even after controlling for sex (male, female), age, education, and occupation (p < .001). More nonwhite patients indicated that additional information would have been helpful in dealing with these concerns (p < .001).ConclusionsNonwhite cancer patients reported more concerns about understanding their diagnosis and treatment plan and were more likely to indicate that additional information would have been helpful. The findings emphasize the need for oncology professionals to confirm patients' understanding and ensure patients' information needs have been met, particularly when working with racial/ethnic minorities.     

HSP90 inhibitor 17AAG causes apoptosis in ATRA-resistant acute promyelocytic leukemia cells

The effects of a novel heat shock protein inhibitor, 17AAG, on established APL cell lines (NB4 and R1) were analyzed. 17AAG induces apoptosis in APL cell lines both sensitive (NB4) and resistant (R1) to ATRA after 72 h of incubation. Apoptosis occurs by a mechanism different than ATRA-mediated response, as the cells do not undergo differentiation before apoptosis. Analysis of bax and bcl-2 shows that pro-apoptotic (bax) and anti-apoptotic (bcl-2) proteins are decreased in expression after incubation with 17AAG. We believe this data supports potential clinical use of agents that target HSP90 in APL patients failing conventional therapy.     

Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin

Cutaneous drug reactions (CDRs) are the most commonly reported adverse drug reactions. These reactions can range from mildly discomforting to life threatening. CDRs can arise either from immunological or nonimmunological mechanisms, though the preponderance of evidence suggests an important role for immunological responses. Some cutaneous eruptions appear shortly after drug intake, while others are not manifested until 7 to 10 days after initiation of therapy and are consistent with delayed-type hypersensitivity. This review discusses critical steps in the initiation of delayed-type hypersensitivity reactions in the skin, which include protein haptenation, dendritic cell activation/migration and T-cell propagation. Recently, an alternative mechanism of drug presentation has been postulated that does not require bioactivation of the parent drug or antigen processing to elicit a drug-specific T-cell response. This review also discusses the role of various immune-mediators, such as cytokines, nitric oxide, and reactive oxygen species, in the development of delayed-type drug hypersensitivity reactions in skin. As keratinocytes have been shown to play a crucial role in the initiation and propagation of cutaneous immune responses, we also discuss the means by which these cells may initiate or modulate CDRs.     

Variable severity of β-thalassemia patients of Eastern India: effect of α-thalassemia and XmnI polymorphism

Sixty-four thalassemia and E-β thalassemia patients were studied for factors that modulate the severity of the disease; i. e., mutation of β-globin gene, presence of α-deletion, and presence of an XnmI site at the −158 position of the Gγ gene. Presence of α-deletion and/or homozygosity for the XmnI site was in general associated with less-severe disease. About 12% of the patients harbored single α-gene deletion, and the gene frequency of the XnmI polymorphism in these patients is 0.48. Received: 16 January 2001 / Accepted: 18 September 2001     

Mechanism of Thimerosal-Induced Structural Destabilization of a Recombinant Rotavirus P[4] Protein Antigen Formulated as a Multi-Dose Vaccine

In a companion paper, a two-step developability assessment is presented to rapidly evaluate low-cost formulations (multi-dose, aluminum-adjuvanted) for new subunit vaccine candidates. As a case study, a non-replicating rotavirus (NRRV) recombinant protein antigen P[4] was found to be destabilized by the vaccine preservative thimerosal, and this effect was mitigated by modification of the free cysteine (C173S). In this work, the mechanism(s) of thimerosal-P[4] protein interactions, along with subsequent effects on the P[4] protein’s structural integrity, are determined. Reversible complexation of ethylmercury, a thimerosal degradation byproduct, with the single cysteine residue of P[4] protein is demonstrated by intact protein mass analysis and biophysical studies. A working mechanism involving a reversible S-Hg coordinate bond is presented based on the literature. This reaction increased the local backbone flexibility of P[4] within the helical region surrounding the cysteine residue and then caused more global destabilization, both as detected by HX-MS. These effects correlate with changes in antibody-P[4] binding parameters and alterations in P[4] conformational stability due to C173S modification. Epitope mapping by HX-MS demonstrated involvement of the same cysteine-containing helical region of P[4] in antibody-antigen binding. Future formulation challenges to develop low-cost, multi-dose formulations for new recombinant protein vaccine candidates are discussed.