Factors Associated with Treatment Satisfaction Among People Living with HIV in Japan and Other Selected Countries: Examination of the Intertwined Roles of Medication, Patient, and Provider Characteristics.

We examined satisfaction and perceived challenges with antiretroviral therapy (ART) among people living with HIV (PLHIV) in Japan vs three other Asian countries (China, Taiwan, South Korea), and 21 non-Asian countries, using data from the 2019 Positive Perspectives Study (pooled sample size from all 25 countries = 2389). Participants in other Asian countries were more likely than those in Japan to report they missed ART ≥ 1 time in the past month because they were depressed/overwhelmed (57.4%[89/155] vs 32.0%[24/75]), had privacy concerns (56.8%[88/155] vs 30.7%[23/75]), were concerned about the potential long-term negative impacts of ART (46.5%[72/155] vs 26.7%[20/75]), or just wanted to forget about HIV (45.8%[71/155] vs 22.7%[17/75]). ART satisfaction however did not differ significantly between surveyed PLHIV in Japan (54.7%[41/75]) vs those in other Asian countries (47.7%[74/155]). The percentage who felt that daily ART dosing limited their lives was 36.0%[27/75] among participants from Japan, 48.4%[75/155] among participants from other Asian countries, and 27.3%[589/2159] among those from non-Asian countries. Within a structural equation model using pooled data from all 25 countries, positive correlations were seen between ART satisfaction and "provider engagement" (ß = 0.35), high perceived control over ART dosing schedule (ß = 0.28), and the belief that ART prevents HIV transmission (ß = 0.16). Conversely, negative correlations were seen between ART satisfaction and experience of ART side-effects (ß = - 0.24), high "ART anxiety" (ß = - 0.20); and being on multi-tablet regimens (ß = - 0.13). Those ART-satisfied reported higher self-rated health and greater ART adherence. These findings underscore the need for patient-centered care to enhance treatment satisfaction and improve ART adherence.

Proteomics-based identification of biomarkers for predicting sensitivity to a PI3-kinase inhibitor in cancer.

To identify biomarkers for predicting sensitivity to phosphatidylinositol 3-kinase (PI3K) inhibitors, we have developed a proteomics-based approach. Using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS), we measured the expression of 393 proteins in 39 human cancer cell lines (JFCR-39), and combined it with our previously established chemosensitivity database to select for proteins whose expressions show significant correlations to drug sensitivities. This integrated approach allowed us to identify peaks from two proteins, 11.6 and 11.8 kDa, that showed significant correlations with the sensitivity to a PI3K inhibitor, LY294002. We found that the 11.8 kDa protein was a phosphorylated form of the 11.6 kDa protein. While the 11.8 kDa protein showed a positive correlation with the sensitivity to LY294002, the 11.6 kDa protein showed a negative correlation with that of the LY294002. The 11.6 kDa protein was purified chromatographically, and was identified by SELDI-TOF MS as the ribosomal P2 protein, which possesses two prospective phosphorylation sites. These results suggested that the phosphorylation status of the ribosomal P2 was responsible for determining the sensitivity to LY294002, and that the ribosomal P2 could be a potential biomarker for predicting chemosensitivity.

Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System.

Hepcidin, a key regulator of iron metabolism, is expressed in the liver, distributed in blood, and excreted in urine. However, to date, no reliable and practical method for measuring the bioactive form of hepcidin in serum has been developed. Here, we used surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) to analyze the distinctive serum proteomic patterns of patients receiving hemodialysis. In the range of 1000 to 15,000 m/z, we found 3 peptides at 2192, 2789, and 2851 m/z that showed a significant correlation with the serum ferritin levels. The molecular sizes of peptides at 2192 and 2789 m/z matched with the reported sizes of hepcidin-20 and -25, respectively, and the serum peptide at 2789 m/z was identified as hepcidin-25 by collision-induced dissociation tandem MS. By using SELDI-TOF MS, we developed a semiquantitative assay for hepcidin-25. In this assay, the level of serum hepcidin-25 correlated well with levels of serum ferritin and serum interleukin-6. Hepcidin-25 was found to accumulate in the serum of patients receiving hemodialysis; this could contribute to the pathogenesis of renal anemia by decreasing the available iron for hematopoiesis. Thus, SELDI-TOF MS would be a clinically useful tool to detect and semiquantify bioactive hepcidin in serum.

Identification of serum proteins related to adverse effects induced by docetaxel infusion from protein expression profiles of serum using SELDI ProteinChip system.

BACKGROUND: For the development of quick and easy methods for screening and identifying treatment-responsive proteins, we determined the protein expression profile of the serum after docetaxel infusion using a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI TOF-MS) system. MATERIALS AND METHODS: Blood from breast cancer patients was collected before and 4, 8, 24 and 48 hours after docetaxel infusion. The protein expression profile was determined by a SELDI TOF-MS system. The relative expression levels of target proteins were compared during the time-course after docetaxel injection. RESULTS: We identified two representative proteins with molecular weights of 7790 Da and 9285 Da. The 7790 Da protein was high molecular weight kininogen, and the 9285 Da protein was apolipoprotein A-II. These two proteins had similar expression patterns in 5 patients, except one patient who experienced severe, acute, adverse effects. CONCLUSION: These results suggest that protein expression profiles determined by SELDI TOF-MS represent useful data for the identification of treatment-responsive proteins.

Rapid discovery and identification of a tissue-specific tumor biomarker from 39 human cancer cell lines using the SELDI ProteinChip platform.

Useful biomarkers are needed for early detection of cancers. To demonstrate the potential diagnostic usefulness of a new proteomic technology, we performed Expression Difference Mapping analysis on 39 cancer cell lines from 9 different tissues using ProteinChip technology. A protein biomarker candidate of 12kDa was found in colon cancer cells. We then optimized the purification conditions for this biomarker by utilizing Retentate Chromatography mass spectrometry (RC-MS). The optimized purification conditions developed "on-chip" were directly transferred to conventional chromatography to purify the biomarker, which was identified as prothymosin-alpha by ProteinChip time-of-flight mass spectrometry (TOF MS) and ProteinChip-Tandem MS systems. The relative expression level of prothymosin-alpha between colon cancer cells and normal colon mucosal cells was evaluated on the same ProteinChip platform. Prothymosin-alpha expression in colon cancer cells was clearly higher than in normal colon cells. These results indicate that prothymosin-alpha could be a potential biomarker for colon cancer, and that the ProteinChip platform could perform the whole process of biomarker discovery from screening to evaluation of the identified marker.