mart-1-antigen and Prostatic-Neoplasms

Perivascular epithelioid cell tumor (PEComa) is a neoplasm chiefly composed of HMB-45-positive epithelioid cells with clear-to-granular cytoplasm and a perivascular distribution. We describe such a tumor involving the prostate and seminal vesicle in a 46-year-old man. The tumor had characteristic histologic features of PEComa. Immunohistochemically, the tumor cells were positive for HMB-45 but negative for epithelial markers, Melan-A, and S100 protein. The tumor behaved in a malignant fashion, and the patient died of the disease 4 years after diagnosis.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Epithelioid Cells; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Prostatic Neoplasms; S100 Proteins; Seminal Vesicles; Smooth Muscle Tumor; Vascular Neoplasms

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96(®) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL responses in vivo.

Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Cancer Vaccines; Cell Line, Tumor; Dendritic Cells; Drug Delivery Systems; Humans; Injections, Intraperitoneal; Lactic Acid; Male; MART-1 Antigen; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Nanomedicine; Nanoparticles; Nanotechnology; Neoplasms, Experimental; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatic Neoplasms; T-Lymphocytes, Cytotoxic

Extra-mammary Paget disease (EMPD) is a rare intra-epithelial carcinoma that is usually found on the apocrine-rich skin of the perineum. We report 2 cases in which EMPD was initially misdiagnosed on the initial punch biopsy as melanoma-in-situ and Bowen disease respectively. Reasons for the misdiagnoses included a rare pigmented axillary variant of EMPD in the first case and atypical bowenoid features on H&E in the second. The cases are described with a critical review of the histopathological findings, along with a review of the current literature. This highlights the necessity of a comprehensive immunohistochemical panel for the assessment of intra-epithelial pagetoid atypical cells.

Topics: Adenocarcinoma; Aged; Biopsy; Bowen's Disease; Carcinoembryonic Antigen; Diagnostic Errors; Humans; Immunohistochemistry; Keratin-7; Male; MART-1 Antigen; Mohs Surgery; Mucins; Neoplasm Grading; Paget Disease, Extramammary; Prostate-Specific Antigen; Prostatic Neoplasms; Skin Neoplasms; Treatment Outcome

Androgen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men.. We used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy.. FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages.. Our results suggest that each of these four genes may play a role, or at least reflect a stage of prostate carcinoma growth/development/progression.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Biomarkers, Tumor; Disease Progression; Fetal Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; MART-1 Antigen; Mice; Microtubule-Associated Proteins; Middle Aged; Models, Biological; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Prostatic Neoplasms; Receptor, Fibroblast Growth Factor, Type 1; WT1 Proteins; Xenograft Model Antitumor Assays

The discovery of human melanoma rejection Ags has allowed the rational design of immunotherapeutic strategies. One such Ag, MART-1, is expressed on >90% of human melanomas, and CTL generated against MART-1(27-35) kill most HLA A2.1(+) melanoma cells. However, variant tumor cells, which do not express MART-1, down-regulate MHC, or become resistant to apoptosis, will escape killing. Cytotoxic lymphocytes kill by two main mechanisms, the perforin/granzyme degranulation pathway and the TNF/Fas/TNF-related apoptosis-inducing ligand superfamily of apoptosis-inducing ligands. In this study, we examined whether cis-diaminedichloroplatinum (II) cisplatin (CDDP) sensitizes MART-1/HLA A2.1(+) melanoma and melanoma variant tumor cells to non-MHC-restricted, Fas ligand (FasL)-mediated killing by CTL. MART-1(27-35)-specific bulk CTL cultures were generated by pulsing normal PBL with MART-1(27-35) peptide. These CTL cultures specifically kill M202 melanoma cells (MART-1(+), HLA A2.1(+), FasR(-)), and MART-1(27-35) peptide-pulsed T2 cells (FasR(+)), but not M207 melanoma cells (MART-1(+), HLA A2.1(-), FasR(-)), FLU(58-66) peptide-pulsed T2 cells, or DU145 and PC-3 prostate cells (MART-1(-), HLA A2.1(-), FasR(+)). CDDP (0.1-10 microg/ml) sensitized non-MART-1(27-35) peptide-pulsed T2 to the CD8(+) subset of bulk MART-1-specific CTL, and killing was abolished by neutralizing anti-Fas Ab. Furthermore, CDDP up-regulated FasR expression and FasL-mediated killing of M202, and sensitized PC-3 and DU145 to killing by bulk MART-1-specific CTL cultures. These findings demonstrate that drug-mediated sensitization can potentiate FasL-mediated killing by MHC-restricted CTL cell lines, independent of MHC and MART-1 expression on tumor cells. This represents a novel approach for potentially controlling tumor cell variants found in primary heterogeneous melanoma tumor cell populations that would normally escape killing by MART-1-specific immunotherapy.

Topics: Adjuvants, Immunologic; Animals; Antigens, Neoplasm; Antineoplastic Agents; Apoptosis; Cells, Cultured; Cisplatin; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Drug Resistance, Neoplasm; Epitopes; Epitopes, T-Lymphocyte; Fas Ligand Protein; fas Receptor; Humans; Hybridomas; Immunization; Major Histocompatibility Complex; Male; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Neoplasm Proteins; Perforin; Pore Forming Cytotoxic Proteins; Prostatic Neoplasms; RNA, Messenger; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Up-Regulation