Proteomics in Melanoma Biomarker Discovery: Great Potential, Many Obstacles

The present clinical staging of melanoma stratifies patients into heterogeneous groups, resulting in the application of aggressive therapies to large populations, diluting impact and increasing toxicity. To move to a new era of therapeutic decisions based on highly specific tumor profiling, the discovery and validation of new prognostic and predictive biomarkers in melanoma is critical. Genomic profiling, which is showing promise in other solid tumors, requires fresh tissue from a large number of primary tumors, and thus faces a unique challenge in melanoma. For this and other reasons, proteomics appears to be an ideal choice for the discovery of new melanoma biomarkers. Several approaches to proteomics have been utilized in the search for clinically relevant biomarkers, but to date the results have been relatively limited. This article will review the present work using both tissue and serum proteomics in the search for melanoma biomarkers, highlighting both the relative advantages and disadvantages of each approach. In addition, we review several of the major obstacles that need to be overcome in order to advance the field

Potential methane and nitrous oxide production and respiration rates from penguin and seal colony tundra soils during freezing–thawing cycles under different water contents in coastal Antarctica

In coastal Antarctica, frequent freezing–thawing cycles (FTCs) and changes to the hydrological conditions may affect methane (CH4) and nitrous oxide (N2O) production and respiration rates in tundra soils, which are difficult to observe in situ. Tundra soils including ornithogenic tundra soil (OAS), seal colony soil (SCS) and emperor penguin colony soil (EPS) were collected. In laboratory, we investigated the effects of FTCs and water addition on potential N2O and CH4 production and respiration rates in the soils. The CH4 fluxes from OAS and SCS were much less than that from EPS. Meanwhile, the N2O fluxes from OAS and EPS were much less than that from SCS. The N2O production rates from all soils were extremely low during freezing, but rapidly increased following thawing. In all cases, FTC also induced considerably enhanced soil respiration, indicating that soil respiration response was sensitive to the FTCs. The highest cumulative rates of CH4, N2O and CO2 were 59.5 mg CH4-C·kg−1 in EPS, 6268.8 μg N2O-N·kg−1 in SCS and 3522.1 mg CO2-C·kg−1 in OAS. Soil water addition had no significant effects on CH4 production and respiration rates, but it could reduce N2O production in OAS and EPS, and it stimulated N2O production in SCS. Overall, CH4 and N2O production rates showed a trade-off relationship during the three FTCs. Our results indicated that FTCs greatly stimulated soil N2O and CO2 production, and water increase has an important effect on soil N2O production in coastal Antarctic tundra

Clinical Utility of Serum Autoantibodies Detected by Protein Microarray in Melanoma

Better prognostic and predictive markers in melanoma are needed to select patients for therapy. We utilized a dual-lectin affinity chromatography and a natural protein microarray-based analysis to select a subproteome of target glycoproteins to profile serum antibodies against melanoma associated antigens that may predict nodal positivity. We identified 5 melanoma-associated antigens using this microarray coupled to mass spectrometry; GRP75, GRP94, ASAH1, CTSD and LDHB. We evaluated their predictive value for nodal status adjusting for age, gender, Breslow thickness, mitotic rate and ulceration using standard logistic regression. After adjustment, ASAH1, CTSD and LDHB were significantly negatively associated with nodal status (P = 0.0008) and GRP94 was significantly positively associated (P = 0.014). Our best multivariate model for nodal positivity included Breslow thickness, presence of serum anti-ASAH1, anti-LDHB or anti-CTSD, and presence of serum anti-GRP94, with an area under the ROC curve of 0.869. If validated, these results show promise for selecting clinically node negative patients for SLN biopsy. In addition, there is strong potential for glycoprotein microarray to screen serum autoantibodies that may identify patients at high risk of distant metastases or those likely or unlikely to respond to treatment, and these proteins may serve as targets for intervention

Temporal and spatial variations of atmospheric methane concentration and δ13 C-CH4 near the surface on the Millor Peninsula, East Antarctica

During the 22nd Chinese Antarctic Research Expedition (CHINARE222, 2005/06) , the atmospheric gas samples near the surface were taken on the Millor Peninsula and adjacent areas, east Antarctica, using Tedlar gas bags. The methane(CH4) concentration and δ13 C-CH4 in those samples were analyzed in the laboratory. The average value of atmospheric CH4 concentration on this peninsula was (1.87 ± 0.12) × 10(-6) , slightly higher than the global average CH4 concentration. The summertime variation of CH4 concentrations showed a large fluctuation, corresponding to the variation of air temperatures. The average δ13 C-CH4 was ( -38.26 ± 0.52) ‰. CH4 concentrations and δ13 C-CH4 at different sites varied from 1.74 × 10(-6) to 2.56 ×10(-6) and from -39.31‰ to - 31.25‰, respectively. The factors affecting CH4 concentrations and δ13 C-CH4 values have also been discussed in this study

B lymphocytes as effector cells in the immunotherapy of cancer

Over the years, the role of B cells in the host immune response to malignancy has been overshadowed by our focus on T cells. Nevertheless, B cells play important roles as antigen‐presenting cells and in the production of antibodies. Furthermore, B cells can function as effector cells that mediate tumor destruction on their own. This review will highlight the various functions of B cells that are involved in the host response to tumor. J. Surg. Oncol. 2012;105:431–435. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90339/1/22093_ftp.pd

Alkaline phosphatase activity in ornithogenic soils in polar tundra

Phosphatase plays an important role in the microbial liberation of phosphorus in soil systems. In this study, alkaline phosphatase activity (APA) was investigated from tundra ornithogenic soil profiles in Antarctica and Arctic. The organic carbon (TOC), total nitrogen (TN), and phosphorus fractions and pH were also analyzed in these soils. The correlation between APA and soil chemical properties is discussed. In almost all the soil profiles, APA showed the same variation patterns. The maximum APA appeared in the surface layers, and decreased with soil depth. The APA ranged from 1.00 ppm to 1 403.5 ppm with an average of approximately 408.3 ppm. The APA showed a significant positive correlation with TOC (r =0.70, p <0.001), TN (r =0.43, p =0.002), total phosphorus (r =0.39, p <0.05)and inorganic phosphorus (r =0.40, p =0.037), indicating that they were predominant factors affecting APA in the polar tundra soils. In addition, APA showed a significant negative correlation with Cu and Zn concentrations in the soils, indicating that Cu and Zn may inhibit APA. Our results showed that APA could be used as an important indicator for soil fertility in polar tundra ecosystems

Ligand-induced unfolding mechanism of an RNA G-quadruplex

The cationic porphyrin, TMPyP4, is a well-established DNA G-quadruplex (G4) binding ligand that can stabilize different topologies via multiple binding modes. However, TMPyP4 has completely opposite destabilizing and unwinding effect on RNA G4 structures. The structural mechanisms that mediate RNA G4 unfolding remains unknown. Here, we report on the TMPyP4-induced RNA G4 unfolding mechanism studied by well-tempered metadynamics (WT-MetaD) with supporting biophysical experiments. The simulations predict a two-state mechanism of TMPyP4 interaction via a groove-bound and a top-face bound conformation. The dynamics of TMPyP4 stacking on the top tetrad disrupts Hoogsteen H-bonds between guanine bases resulting in the consecutive TMPyP4 intercalation from top-to-bottom G-tetrads. The results reveal a striking correlation between computational and experimental approaches and validate WT-MetaD simulations as a powerful tool for studying RNA G4-ligand interactions

Germline-Encoded TCR-MHC Contacts Promote TCR V Gene Bias in Umbilical Cord Blood T Cell Repertoire.

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the "net" genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR β chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires