Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

Role of arthrography in imaging of the temporomandibular joint in 1992]

In this text we briefly want to discuss the role of the arthrographic examination of the temporomandibular joint for detection of disc pathology. We will mention the normal anatomy and function of the temporomandibular joint, the technique for performing arthrograms and the classification of the most frequent disc pathology. This will be illustrated by some arthrographic examples of anterior disc displacement without reduction, disc perforation, and medial disc displacement. Finally the advantages of arthrography in comparison with other investigation techniques will be discussed.     

Monoclonal antibodies against respiratory syncytial virus and their use for rapid detection of virus in nasopharyngeal secretions.

We developed five monoclonal antibodies against respiratory syncytial virus. Three of these (23A3, 12A4, and 18B2) were used in an indirect fluorescent antibody test, and the results were compared with those of a similar indirect fluorescent test with commercial anti-respiratory syncytial virus serum. The results obtained with antibody 18B2 and commercial anti-respiratory syncytial virus serum were identical, whereas with antibodies 23A3 and 12A4 the incidence of positive identifications was around 50%.     

Cyclooxygenase-2 in normal,hyperplastic and neoplastic follicular cells of the human thyroid gland

This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p0.05). However, we could not establish any relationships among COX-2, patients ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies.     

Microsatellite alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

A series of 20 hepatocellular carcinomas and 8 intrahepatic cholangiocarcinomas was screened from the Korean population for microsatellite alterations, including a loss of heterozygosity and replication errors using nine microsatellite markers containing several genes. The microsatellite results and our previous comparative genomic hybridization results of two tumors were compared at each locus, and the correlations between these and clinicopathologic variables were examined. The most characteristic findings were found at 13q. Replication errors were prevalent at D13S160 (13q21.2 approximately q31) and D13S292(13q12). The incidence of loss of heterozygosity, however, was higher at D13S153 (13q14.1 approximately q14.3) and D13S265(13q31 approximately q32). In contrast, there were higher deletion frequencies observed in hepatocellular carcinoma (HCC) and higher amplification frequencies observed in intrahepatic cholangiocarcinoma at 13q in our previous comparative genomic hybridization (CGH) study. Higher frequencies of replication errors were observed at D16S408 (13q12 approximately q21) and D16S504(13q23 approximately q24) in the HCC. This study found that significant differences in the patterns of genetic instability of microsatellites were dependent on the chromosomal loci. It is believed that certain genes at altered CGH regions, which are relevant to the development and/or progression of these cancers, are activated by different mutation mechanisms.     

Self-assembly of in vitro-translated human papillomavirus type 16 L1 capsid protein into virus-like particles and antigenic reactivity of the protein.

The human papillomavirus type 16 (HPV-16) L1 capsid protein is the major component of the HPV virion. We prepared L1 protein of HPV-16 in a cell-free system. The L1 gene was cloned in an expression plasmid and transcribed and translated in vitro in a rabbit reticulocyte lysate. The expressed protein had the molecular mass (55 kDa) expected for the L1 protein, and it assembled into virus-like particles that closely resembled papillomavirus virions. The protein retained conformational epitopes, as evidenced by its reactivity with monoclonal antibodies which recognize only intact viral particles. In radioimmunoprecipitation assays with sera from college women grouped by their genital tract HPV DNA status, high reactivity was found in 68% of HPV-16 DNA-positive women, in 23% of women with other HPVs, and in 19% of HPV-negative women. In comparison, none of the sera of children were reactive. The results of the radioimmunoprecipitation assays showed a significant correlation with results obtained with the same sera in an enzyme-linked immunosorbent assay with virus-like particles produced in baculovirus (chi-square test for linear trend, P = 0.0023). Although the amounts of L1 protein obtained are small, the ability to produce virus-like particles by in vitro translation may be useful in the study of virus assembly, virus binding, and the immunological response to HPV infection.     

Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells

Despite numerous reports on MHC class II expression by T cells from a wide spectrum of mammalian species including humans, the biological relevance of this phenomenon has never been tested with appropriately designed animal models. To address this issue, we developed mouse models in which immature thymocytes are the only positively selecting antigen-presenting cells in the thymus. In these mice, CD4+ T cells were generated with the appropriate maturation phenotype and showed a diverse repertoire of TCR Vbetas. The CD4+ T cells were functionally competent, mediating effective allogeneic responses that involved polyclonal TCR Vbetas. These results suggest that the thymocyte-thymocyte (T-T) interaction operates as an independent pathway for CD4+ T cell selection in the thymi of species with MHC II-positive thymocytes. This T-T interaction appears to be the basis for the generation of donor MHC-restricted CD4+ T cells in xenogeneic hosts.     

Effects of apatite and wollastonite containing glass-ceramic powder and two types of alumina powder in composites on osteoblastic differentiation of bone marrow cells

Previously we developed a composite consisting of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyldimethacrylate (Bis-GMA)-based resin (designated AWC), and demonstrated that AWC showed direct contact with living bone. Another new composite consisting of mainly the delta-crystal phase of alumina bead powder and Bis-GMA-based resin (designated ABC) was developed. Although alumina ceramics are bioinert and a composite filled with the pure alpha-crystal phase of alumina powder (designated alphaALC) did not allow direct bone formation in vivo, ABC was shown to have excellent osteoconductivity. One purpose of this study was to investigate whether AW-GC powder in a composite promotes osteoblastic differentiation of rat bone marrow cells as AW-GC bulk did. Another purpose was to evaluate the effects of the delta-crystal phase of alumina powder in a composite on osteoblastic differentiation. In a cell culture with dexamethasone, alkaline phosphatase (AP) activity at both days 7 and 14, and the levels of osteocalcin mRNA and alpha1(I) collagen mRNA at day 14 and osteopontin mRNA at day 7, were highest on AWC, followed by ABC, and finally alphaALC. Scanning electron microscopy showed more abundant mineralized globules and a fibrous collagen matrix on AWC at day 14, followed by ABC. In a cell culture without dexamethasone, AP activity at both days 7 and 14, and the level of osteopontin mRNA at day 7, were higher on ABC than on any other composite, whereas osteocalcin mRNA could not be detected. These results indicate that AW-GC powder in a composite promotes osteoblastic differentiation of bone marrow cells intensively when supplemented with dexamethasone. The delta-crystal phase of alumina powder in a composite promotes greater osteoblastic differentiation than the alpha-crystal phase of alumina powder.     

Does multidetector computed tomographic urography (MDCTU) T staging classification correspond with pathologic T staging in upper tract urothelial carcinoma?

International Urology and Nephrology - Multidetector computed tomographic urography (MDCTU) is not yet sufficient to be used in the clinical staging of upper tract urothelial carcinoma (UTUC). This...