Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia.

The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied.

Decreased levels of CD44 protein and mRNA in prostate carcinoma. Correlation with tumor grade and ploidy.

Background: CD44, a transmembrane protein, is associated with cell-cell and cell-matrix interaction and with tumor growth and metastasis. Expression of both standard form and variant isoforms of CD44 protein has been associated with aggressive behavior and metastasis in various tumors, but has not been characterized in prostate adenocarcinoma (PAC).

Methods: The expression of CD44 standard (CD44s) and splice variant v3, v4/5, v6, v7/8, and v10 proteins were studied in 109 PACs and correlated with tumor grade, DNA ploidy, and mRNA levels.

Expression of cytochromes P450 in human breast tissue and tumors.

In an effort to determine which members of the cytochrome P450 (CYP) superfamily are expressed in human breast tissue and tumors, RNA-polymerase chain reaction studies have been undertaken. Detection of expressed CYP mRNAs identifies those forms of the enzyme that are capable of expression in breast tissue, and provides insight into the potential for in situ xenobiotic and therapeutic drug metabolism. CYP1A1 mRNA was present in (5/11) breast tissues and (6/13) tumors.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate and 17 beta-estradiol on estrogen receptor regulation in MCF-7 human breast cancer cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exhibits remarkably potent antiestrogenic activity. To further elucidate the role of estrogen receptor (ER) regulation in this response, we examined the effects of exposure to TCDD in MCF-7 human breast cancer cells on ER mRNA levels by using an RNase protection assay, on ER accumulation by using an ER immunocytochemical essay (ER-ICA), and on ER function by competitive binding assays under conditions of saturating 17 beta-estradiol (E2). Comparative studies were conducted with E2 and 12-O-tetradecanoylphorbol-13-acetate (TPA), as both compounds are known to suppress ER expression.

Increased bcl-2 protein levels in prostatic adenocarcinomas are not associated with rearrangements in the 2.8 kb major breakpoint region or with p53 protein accumulation.

bcl-2, an inhibitor of programmed cell death (apoptosis), is present in high levels in a subset of prostatic adenocarcinomas. In this study, 42 prostatic adenocarcinomas were analyzed to determine whether increased bcl-2 levels are associated with rearrangements in the 2.8-kb major breakpoint region, an association known to occur in certain follicular lymphomas featuring a t(14:18) translocation.

Multivariate survival analysis of clinicopathologic features in surgical stage I endometrioid carcinoma including analysis of HER-2/neu expression.

Objective: We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma.

Study Design: Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clincopathologic features, deoxyribonucleic acid ploidy, and HER-2/neu expression.

E-cadherin expression in papillary transitional cell carcinoma of the urinary bladder.

E-cadherin (E-CD), a cell adhesion molecule that plays a diverse role in cell-cell and cell-matrix interaction, has recently been associated with tumor invasion and metastasis. We evaluated the E-CD expression in 55 cases of urinary bladder papillary transitional cell carcinoma using a double-linked immunoalkaline phosphatase procedure on formalin-fixed, paraffin-embedded specimens quantified as percentage positive staining area with the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). The 10 grade I tumors stained intensely for E-CD (66%) and showed enhanced staining compared with normal transitional epithelium.

Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies. Correlation with tumor grade, stage, PSA level, and DNA ploidy status.

National screening programs resulting in an increased detection rate of prostatic adenocarcinoma have prompted the search for new methods of predicting disease outcome that can be applied to the initial narrow bore needle biopsy specimens. Cathepsin D, a lysosomal aspartyl protease and autocrine mitogen, has been studied in a wide variety of human neoplasms as an invasion and metastasis marker. Prostatic carcinoma needle biopsy tumor cell cathepsin D content was measured in 61 men using a semiquantitative image analysis assisted immunohistochemical procedure.

Nuclear p53 immunoreactivity in papillary thyroid cancers is associated with two established indicators of poor prognosis.

The tumor suppressor protein, p53, protects somatic cells against the accumulation of genomic alterations. Cells harboring mutant or inactivated wild-type p53 protein are at risk for the development of genomic instability. Nuclear accumulation of p53 protein is associated with the stepwise dedifferentiation of papillary carcinoma.

Quantitative RNA-polymerase chain reaction-DNA analysis by capillary electrophoresis and laser-induced fluorescence.

Quantitative RNA-polymerase chain reaction (RNA-PCR) is an extremely powerful analytical tool owing to its specificity and high level of sensitivity. Quantitative RNA-PCR is, however, highly labor intensive. No analytical method currently exists that can accurately and rapidly quantitate the small quantities of DNA in RNA-PCR reaction mixtures.

Alteration of the p53 locus in benign hyperplastic prostatic epithelium associated with high-grade prostatic adenocarcinoma.

Recent evidence suggests that the tumor suppressor protein, p53, protects somatic cells against the accumulation of genomic mutations. The genomes of cells lacking normal p53 function may become hypermutable, a condition that might result in the accumulation of multiple genetic alterations as the affected cells proliferate. Such cells may then become more susceptible to malignant transformation.

Prediction of pathologic stage and postprostatectomy disease recurrence by DNA ploidy analysis of initial needle biopsy specimens of prostate cancer.

Background: DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound-guided needle biopsies has not been studied extensively.

Methods: Eighty-nine paired needle biopsy specimens (NBX) and radical prostatectomy (RPX) specimens from patients with early clinical stage (A2-B2) prostate cancer were evaluated for DNA content by image analysis of Feulgen stained tissue sections. Findings were compared with Gleason grading on the same specimens by univariate and multivariate analyses for prediction of local tumor invasion, metastasis, disease recurrence, and serum prostate specific antigen concentration during a 0.

E-cadherin expression in prostatic carcinoma biopsies: correlation with tumor grade, DNA content, pathologic stage, and clinical outcome.

We compared tumor grade and DNA content with expression of E-cadherin (E-CD), a cell adhesion molecule associated with cell-cell and cell-matrix interaction, leukocyte function, and tumor invasion and metastases, on 56 prostate carcinoma needle biopsies. The findings were correlated with final pathologic stage at subsequent prostatectomy, preoperative serum prostate-specific antigen level and further development of metastases during an initial 2.4-yr mean clinical follow-up period (range 0.

Observations on tumor and metastatic suppressor gene status in endometrial carcinoma with particular emphasis on p53.

Background: Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23-H1.

Methods: The status of the p53 gene was studied by immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72 patients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patients with benign endometria.

Association of p53 immunoreactivity with high gleason tumor grade in prostatic adenocarcinoma.

To determine whether p53 immunoreactivity correlates with the Gleason tumor grade in primary adenocarcinoma of the prostate we analyzed 107 consecutive surgical specimens (78 radical prostatectomies and 29 transurethral resections). A hematoxylin-eosin-stained slide from a representative block of each tumor was examined, and primary and secondary Gleason scores were assigned in each case. Additional paraffin sections from the same block were stained immunohistochemically for p53 expression using the monoclonal antibody clone DO-1, a mouse IgG2a directed against a denaturation-resistant epitope of p53.

Contribution of HER-2/neu oncogene expression to tumor grade and DNA content analysis in the prediction of prostatic carcinoma metastasis.

Background: Recent advances in the early detection of prostatic adenocarcinoma have stimulated interest in the development of techniques for determining metastatic potential.

Methods: One hundred cases of adenocarcinoma, including 66 biopsy and radical prostatectomy specimens; 20 biopsies alone; and 14 transurethral resection specimens, were evaluated for Gleason tumor grade, DNA content and HER-2/neu expression. DNA content was determined on Feulgen-stained touch preparations and tissue sections (18 cases) or tissue sections alone.

Recent advances in diabetes care and management.

Four developments in diabetes care and management have evolved over the last decade and are now routinely incorporated into clinical practice: (1) the introduction of recombinant human insulin; (2) the use of second generation oral agents; (3) home glucose monitoring and glycohemoglobin monitoring; and (4) a better understanding of the relationship between diabetic control and complications.

Treatment of snakebite poisoning.

The epidemiology, mechanics, prevention, pharmacology, clinical manifestations, and treatment of snakebites are reviewed. Poisonous snakes bite approximately 8000 persons annually in the United States, causing approximately 12-15 deaths per year. Pit vipers (rattlesnakes, copperheads, cottonmouths, and massasaugas) are responsible for 99% of all snakebite poisonings; coral snakes and other foreign exotic species are responsible for the additional 1%.

Drug usage evaluation: H2-receptor antagonist use in 30 hospitals.

In this 30-hospital survey, data on usage, adverse drug reaction (ADR) rates, and drug interactions (DI) of the H2-receptor antagonists (H2RA) cimetidine, ranitidine, and famotidine were analyzed. Approximately 8% (1,768 patients) admitted to participating hospitals received an H2RA (range: 0.5 to 30%).

The effects of amiodarone on thyroid hormone function: a review of the physiology and clinical manifestations.

Amiodarone, an iodinated benzofuran derivative, is used for treatment of refractory cardiac arrhythmias. Certain features of the drug's structure resemble those of the biologically active thyroid hormone, triiodothyronine (T3). In addition, the drug has a variety of complex effects on thyroid hormone physiology, including a number of possible antagonistic effects on thyroid hormone function at the cellular level.