Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells

Vaccine therapy for prostate and breast cancer may have potential for treating these major causes of death in males and females, respectively. Critical to the development of tumor-specific vaccines is finding and characterizing novel antigens to be recognized by CD8(+) T cells. To define new CD8(+) T-cell tumor antigens, we determined two wild-type HLA-A2 epitopes from a recently found tumor-associated protein, TARP (T-cell receptor gamma alternate reading frame protein), expressed in prostate and breast cancer cells. We were also able to engineer epitope-enhanced peptides by sequence modifications. Both wild-type and enhanced epitopes induced peptide-specific CD8(+) T-cell responses in A2K(b) transgenic mice. In vitro restimulation of human CD8(+) T cells from a prostate cancer patient resulted in CD8(+) T cells reactive to the peptide epitopes that could lyse HLA-A2(+) human breast cancer cells (MCF-7) expressing TARP. Epitope-specific human CD8(+) T cells were also enumerated in patients' peripheral blood by tetramer staining. Our data suggest that HLA-A2-binding TARP epitopes and enhanced epitopes discovered in this study could be incorporated into a potential vaccine for both breast and prostate cancer.     

A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype

A novel protein MGC5306 has been identified in yeast-two-hybrid analysis by screening a HeLa cDNA library with a truncated DNA polymerasebeta (polbetaDelta) as bait. The polbetaDelta is expressed in various types of cancers. Co-immunoprecipitation-Western blot analysis confirms not only its interaction with polbetaDelta but also with wild-type polbeta. Binding to polbeta indicates potential function of MGC5306 in repair pathway. Transfection of cells with MGC5306-GFP and Western blot analysis with anti-MGC5306 antibody reveal its nuclear localization. MGC5306 is expressed in human carcinomas and tumor cell lines but not in normal tissues, suggesting MGC5306 is most likely involved in carcinogenesis. An antigrowth activity and modulations of cell cycle events are identified in cells expressing siRNAMGC5306.     

Peripheral Nerve Tumors: Management Strategies and Molecular Insights

Because of its relative rarity and a wide variety of clinical manifestations, peripheral nerve tumors (PNTs) often present to specialists from widely different disciplines, thus often resulting in delayed diagnosis and a non-cohesive pattern of management. Critical appraisal of the history and physical examination followed by radiological investigations, by experienced medical personnel, ultimately suggests that the extremity mass is perhaps a PNT, rather than the wide variety and more common soft tissue tumors. Included in this appraisal is a search for a pre-disposition syndrome, the most common of which are neurofibromatosis-1 and -2 (NF1, NF2) and schwannomatosis, which may require life-long careful follow up. Intra-operative and post-operative management decisions in a multidisciplinary manner with knowledge of the biological, pathological and clinical behavior of the PNT, is of utmost importance. In the context of pre-disposition syndromes, where multiple tumors may exist along with other nervous system lesions, molecular biological insights and hopefully the biological therapies that stem from this knowledge are of interest. In this article the spectrum of PNTs and their management protocols, including the algorithm for treatment of malignant PNTs advocated by our institute, are presented and currently available genetic insights and probable role of experimental therapies are briefly reviewed.     

Percutaneous penetration and genotoxicity of 4,4'-methylenedianiline through rat and human skin in vitro

4,4'-Methylenedianiline (MDA) is a primary aromatic amine used in the plastics industry and is classified by the International Agency for Research on Cancer as an animal carcinogen and possible human carcinogen. In order to estimate human exposure it is useful to determine percutaneous penetration. Previous studies have suggested that both rat and human skin were permeable to MDA, with greater penetration being seen through human skin. In this study no significant difference was seen between the percutaneous penetration of MDA through human or rat skin for three different treatment levels: 0.01, 0.1 and 1mg per skin membrane (0.32 cm(2)). The apparent dermal flux was calculated as 0.7 +/- 0.3 and 10.1 +/- 2.0 microg/cm(2)/h for the 0.01 and 0.1mg treatments, respectively. The permeability constant K(p) was estimated at 1.8 x 10(-3) cm/h and the lag time at 3.5 +/- 0.5 h. MDA absorbed into the skin was found to be bioavailable. Experiments also showed that after application of 0.1mg MDA, 4% penetrated through latex and nitrile gloves, respectively. The potential genotoxicity of MDA in human skin was assessed by DNA (32)P-postlabelling; levels of DNA adducts were detected, following the treatment and penetration of 1mg MDA.     

Uranotaenia dibrugarhensis, a new species in subgenus Pseudoficalbia from Assam, India

The adult female, adult male, pupa, and larva of Uranotaenia (Pseudoficalbia) dibrugarhensis, new species, are described from the Dibrugarh District of Assam State, India.     

Diagnosis of pancreatic cancer using serum proteomic profiling

In the United States, mortality rates from pancreatic cancer (PCa) have not changed significantly over the past 50 years. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. The objective of this study was to use high-throughput protein profiling technology to identify biomarkers in the serum proteome for the early detection of resectable PCa. Using surface-enhanced laser desorption/ionization mass spectrometry, protein profiles were generated from sera of 49 PCa patients and 54 unaffected individuals after fractionation on an anion exchange resin. The samples were randomly divided into a training set (69 samples) and test set (34 samples), and two multivariate analysis procedures, classification and regression tree and logistic regression, were used to develop classification models from these spectral data that could distinguish PCa from control serum samples. In the test set, both models correctly classified all of the PCa patient serum samples (100% sensitivity). Using the decision tree algorithm, a specificity of 93.5% was obtained, whereas the logistic regression model produced a specificity of 100%. These results suggest that high-throughput proteomics profiling has the capacity to provide new biomarkers for the early detection and diagnosis of PCa.     

Nodal metastasis in major salivary gland cancer: predictive factors and effects on survival

OBJECTIVES: To determine how regional nodal metastasis affects survival in patients with major salivary gland malignancy and to identify clinical predictors for nodal disease. METHODS: Major salivary gland cancer cases with nodal sampling were identified from the Surveillance, Epidemiology, and End Results cancer database for 1988 through 1998. Kaplan-Meier survival analysis was conducted to compare patients with and without histopathologic evidence of nodal disease. Multivariate logistic regression analysis was used to determine the influence of clinical predictors on the presence of regional nodal disease. RESULTS: A total of 1268 patients with major salivary gland malignancy and regional node sampling were identified. Mean age at diagnosis was 58.3 years, with a male-female ratio of 1:4. Mean tumor size was 3.0 cm. Overall mean survival time was 83 months (95% confidence interval, 80-87 months). Patients with no evidence of nodal cancer had significantly improved survival over patients with any pathologically positive nodes (mean survival time, 100 months vs 59 months, respectively; P<.001). Patient age, tumor histopathologic type, facial nerve involvement, extraglandular involvement, tumor grade, and tumor size were significant clinical predictors of nodal disease. Facial nerve involvement, tumor grade, and squamous cell carcinoma subtype exhibited the highest increased odds ratios for nodal metastasis. CONCLUSIONS: Nodal disease significantly decreases survival in patients with major salivary gland malignancy. Tumor histopathologic type, facial nerve involvement, extraglandular tumor extension, and tumor grade are the most important predictors of nodal disease.     

Bacterial colonization of nasal steroid inhalers in chronic rhinosinusitis

BACKGROUND: The aim of this study was to determine if nasal steroid inhalers harbor bacteria. METHODS: Nasal steroid inhalers were randomly selected from an adult patient population with chronic rhinosinusitis. Swab cultures of the tip of the nasal inhaler were obtained and submitted for microbiological analysis. Contemporaneous control cultures were obtained from freshly opened nasal steroid inhalers. Comparisons were conducted between bacterial recovery rates and types of organisms recovered from the patient and control groups. RESULTS: Among 31 nasal inhalers in use, 14 inhalers (45%) were found to harbor bacteria. The most common organisms were coagulase negative Staphylococci (11 inhalers) followed by oral flora (2 inhalers) and bacillus species (1 inhaler). None of the 10 control cultures were found to harbor bacteria. Nasal steroid inhalers in use were more likely to have bacterial colonization than new inhalers (p = 0.008, chi-square). CONCLUSIONS: Nasal steroid inhalers may harbor pathogenic bacteria. Therefore, they may serve as a vehicle for subsequent reinfection.