Immunohistochemical evaluation of necrotic malignant melanomas.

We evaluated 35 cases of malignant melanomas with substantial necrosis immunostained with S-100, HMB-45, Melan-A, tyrosinase, PNL2, and microphthalmia transcription factor (MITF). Staining patterns were evaluated in viable and necrotic areas of the tumors. S-100 was the most sensitive marker (97%) in the viable tumors, but necrotic areas demonstrated nonspecific staining.

The expression and function of androgen receptor coactivator p44 and protein arginine methyltransferase 5 in the developing testis and testicular tumors.

Purpose: The role of androgen receptor coactivators in testicular development and cancer formation is unclear. p44/Mep50 was identified as an androgen receptor coactivator that functions in a complex with protein arginine methyltransferase 5. We studied the expression of p44 and protein arginine methyltransferase 5 in developing fetal testis and adult testicular tumors, including seminomas and Leydig cell tumors.

Practical aspects of planning, building, and interpreting tissue microarrays: the Cooperative Prostate Cancer Tissue Resource experience.

This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using radiographs of original paraffin blocks to measure tissue thickness we developed a method to produce TMAs with a larger number of usable sections.

A potent and orally active HIV-1 integrase inhibitor.

A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with excellent inhibitory activity in cells, good pharmacokinetics, and an excellent ability to inhibit virus with mutant enzyme.

Total synthesis of (-)-normalindine via addition of metalated 4-methyl-3-cyanopyridine to an enantiopure sulfinimine.

A concise total asymmetric synthesis of the tetrahydronaphthyridine alkaloid (-)-normalindine has been accomplished via the addition of a laterally metalated 4-methyl-3-cyanopyridine to a sulfinimine (N-sulfinyl imine) as the key step.

Regulation of androgen receptor activity by tyrosine phosphorylation.

The androgen receptor (AR) is essential for the growth of prostate cancer cells. Here, we report that tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors. Mutation of the major tyrosine phosphorylation site in AR significantly inhibits the growth of prostate cancer cells under androgen-depleted conditions.

Primary aldosteronism caused by unilateral adrenal hyperplasia.

In the hypertensive population, primary aldosteronism has been reported to have a prevalence of 0.1% to 2%, with the main causes being aldosterone-producing adenomas and bilateral hyperplasia. However, there is a third rare entity, called unilateral adrenal hyperplasia, that contributes to primary aldosteronism.

[In vitro adherence of Staphylococcus epidermidis and Pseudomonas alcaligenes to intraocular lenses].

Purpose: To quantify and compare the in vitro adherence of Staphylococcus epidermidis and Pseudomonas alcaligenes to different intraocular lenses (IOLs).

Methods: Fourteen intraocular lenses were used in the experiment. Four of polymethylmethacrylate (PMMA), four of silicone, four of hydrogel and two of acrylic.

Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse.

The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human prostate xenograft CWR22. Here, we report that Etk is up-regulated in human prostate tumor specimens surveyed. Knocking down Etk expression by a specific small interfering RNA (siRNA) in prostate cancer cells attenuates cell proliferation, suggesting an essential role of Etk for prostate cancer cell survival and growth.

Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland.

Androgen receptor (AR) is a ligand-activated transcription factor that mediates the action of androgens and is essential for the growth, function, and cell differentiation of the prostate gland. Here, we demonstrated that the prostate apoptosis response factor-4 (par-4) functions as a novel AR coactivator. Par-4 physically interacted with the DNA-binding domain of AR, enhanced AR interaction with DNA, and increased AR-dependent transcription.

An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

Background: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control.

Optic nerve changes in ocular toxoplasmosis.

Purpose: To determine the prevalence and features of the different types of involvement of the optic nerve in ocular toxoplasmosis.

Methods: Retrospective cross-sectional study. All patients with active ocular toxoplasmosis, consulting in the Uveitis Section of the Ophthalmology Department were selected.

PAX2: a reliable marker for nephrogenic adenoma.

Nephrogenic adenoma is a rare lesion of the urinary tract. The diagnosis usually is straightforward when characteristic microscopic and clinical findings are present, and the entity is familiar. However, misdiagnosis, in particular of adenocarcinoma of the prostate gland, may occur.

Cell-specific regulation of androgen receptor phosphorylation in vivo.

The biological ramifications of phosphorylation of the androgen receptor (AR) are largely unknown. To examine the phosphorylation of AR at serine 213, a putative substrate for Akt, a phosphorylation site-specific antibody was generated. The use of this antibody indicated that AR Ser-213 is phosphorylated in vivo and that phosphorylation is tightly regulated in a cell type-specific manner.

Ethnic differences in expression of the dysregulated proteins in uterine leiomyomata.

Background: Black ethnicity is one of the risk factors for uterine leiomyomata (ULM). Little is known about the ethnic differences in leiomyoma-associated gene products in women with uterine leiomyomata.

Methods: A total of 120 hysterectomies with ULM were collected from black, Asian, Hispanic and white women (30 cases from each group).

The development of common data elements for a multi-institute prostate cancer tissue bank: the Cooperative Prostate Cancer Tissue Resource (CPCTR) experience.

Background: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers.

Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases.

Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of spindle cells. Only a few cases arising in the penis have been reported. The aim of this study is to better define the clinicopathologic features of this neoplasm.

Stromal cell-derived factor-1alpha and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma: von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor.

The genetic hallmark of hemangioblastomas and clear cell-renal cell carcinomas (CC-RCCs) is loss-of-function of the von Hippel-Lindau (VHL) tumor suppressor protein. VHL is required for oxygen-dependent degradation of hypoxia-inducible factor-1alpha (HIF-1alpha). In hemangioblastomas and CC-RCCs, HIF-1alpha is constitutively overexpressed leading to increased transcription of HIF-1-regulated genes, including vascular endothelial growth factor (VEGF).

Expression of androgen receptor associated protein 55 (ARA55) in the developing human fetal prostate.

Purpose: Development and differentiation of the human fetal prostate are androgen dependent and follow a specific pattern of solid bud-ductal morphogenesis, which involves stromal-epithelial interactions. Androgen receptor associated protein 55 (ARA55) an androgen receptor coactivator localized in stromal cells, binds to androgen receptor (AR) and regulates androgen receptor translocation and transcriptional activity. We investigated whether ARA55 has a role in human prostate development.

Prostate cancer in patients with screening serum prostate specific antigen values less than 4.0 ng/dl: results from the cooperative prostate cancer tissue resource.

Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.

The cooperative prostate cancer tissue resource: a specimen and data resource for cancer researchers.

Purpose: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a National Cancer Institute-supported tissue bank that provides large numbers of clinically annotated prostate cancer specimens to investigators. This communication describes the CPCTR to investigators interested in obtaining prostate cancer tissue samples.

Experimental Design: The CPCTR, through its four participating institutions, has collected specimens and clinical data for prostate cancer cases diagnosed from 1989 onward.

The tissue microarray data exchange specification: implementation by the Cooperative Prostate Cancer Tissue Resource.

Background: Tissue Microarrays (TMAs) have emerged as a powerful tool for examining the distribution of marker molecules in hundreds of different tissues displayed on a single slide. TMAs have been used successfully to validate candidate molecules discovered in gene array experiments. Like gene expression studies, TMA experiments are data intensive, requiring substantial information to interpret, replicate or validate.

Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients.

Purpose: The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds.

Experimental Design: Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined.