Management of patients with cystic fibrosis and allergic bronchopulmonary aspergillosis using anti-immunoglobulin e therapy (omalizumab).

Omalizumab is a recombinant DNA-derived humanized immunoglobulin G (IgG) anti-IgE monoclonal antibody approved for use in patients with allergic asthma. However, it is not approved for allergic bronchopulmonary aspergillosis (ABPA). Conflicting reports exist about the effects of omalizumab on ABPA in patients with cystic fibrosis (CF).

Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes.

High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague-Dawley rat and human (both male and female) hepatocytes for 72 h with 0-1000 microM Pyrethrins and 0-1000 microM Phenobarbital did not result in any marked cytotoxicity.

Creation and characterization of a doxycycline-inducible mouse model of thyroid-targeted RET/PTC1 oncogene and luciferase reporter gene coexpression.

Background: RET/PTC1 chromosomal rearrangement is associated with papillary thyroid carcinoma formation in children exposed to ionizing radiation. We previously created a transgenic mouse model with thyroid-targeted constitutive RET/PTC1 expression and demonstrated papillary thyroid carcinoma formation.

Objective: In this study, we aimed to create a doxycycline-inducible mouse model of thyroid RET/PTC1 and luciferase reporter gene coexpression to allow for noninvasive monitoring of transgene expression in mice of various ages and timepoints after induction.

PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer.

Background: The sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability.

Pheochromocytoma in an aged female African elephant (Loxodonta africana).

A 43 yr-old female African elephant (Loxodonta africana) collapsed acutely and died. Necropsy revealed an enlarged right adrenal medulla. Histologic appearance was typical of pheochromocytoma.

Genetic alterations in thyroid cancer: the role of mouse models.

Thyroid carcinomas are the most common endocrine neoplasms in humans, with a globally increasing incidence. Thyroid follicular cells and neuroendocrine (parafollicular) C cells are each susceptible to neoplastic transformation, resulting in thyroid cancers of differing phenotypes with unique associated genetic mutations and clinical outcomes. Over the past 15 years, several sophisticated genetically engineered mouse models of thyroid cancer have been created to further our understanding of the genetic events leading to thyroid carcinogenesis in vivo.

A mode of action for induction of liver tumors by Pyrethrins in the rat.

High doses of Pyrethrins produce liver tumors in female rats. To elucidate the mode of action for tumor formation, the hepatic effects of Pyrethrins have been investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats' diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and 42 days followed by 42 days of reversal.

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.

Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal.

Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in a 2-year carcinogenicity study is consistent with a rat-specific mechanism of thyroid neoplasia.

The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control), 0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the treatment, increased incidences of thyroid follicular cell hyperplasia and neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There were no other treatment-related effects and no tumors at other sites.

Primary care physicians' awareness and adherence to cervical cancer screening guidelines in Texas.

Background: Cervical cancer screening guidelines were created to help healthcare professionals in appropriate screening utilizing the PAP test. However, significant variation in cervical cancer screening among primary care physicians has been noted. Knowledge of the awareness of and adherence to cervical cancer screening guidelines by primary care physicians will help determine how best to disseminate and educate these physicians regarding the guidelines in hopes of reducing unnecessary screening and improving screening for under screened populations.

Effects of calcitriol, seocalcitol, and medium-chain triglyceride on a canine transitional cell carcinoma cell line.

Background: Transitional cell carcinoma (TCC) in dogs is associated with high morbidity and mortality. Calcitriol and its analog seocalcitol, combined with medium-chain triglyceride (MCT), have potential for the treatment of this disease.

Materials And Methods: TCC cells were treated with calcitriol or seocalcitol, alone or combined with MCT.

Mechanisms of hormone-mediated carcinogenesis of the ovary.

Experimental ovarian carcinogenesis has been investigated in inbred and hybrid strains of mice and induced by a diversity of mechanisms including X-irradiation, oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic sites, neonatal thymectomy, mutant genes reducing germ cell populations, and aging. Disruptions in the function of graafian follicles by a variety of mechanisms results in a spectrum of ovarian proliferative lesions, including tumors. The findings in mutant and genetically engineered mice support the concept of a secondary (hormonally mediated) mechanism of ovarian tumorigenesis in mice associated with sterility.

Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer.

The sodium/iodide symporter (NIS) is a membrane transport glycoprotein normally expressed in the thyroid gland and lactating mammary gland. NIS is a target for radioiodide imaging and therapeutic ablation of thyroid carcinomas and has the potential for similar use in breast cancer treatment. To facilitate NIS-mediated radionuclide therapy, it is necessary to identify signaling pathways that lead to increased NIS expression and function in breast cancer.

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species.

Effects of 1,25(OH)2D3, 25OHD3, and EB1089 on cell growth and Vitamin D receptor mRNA and 1alpha-hydroxylase mRNA expression in primary cultures of the canine prostate.

The aim of this study was to investigate effects of 1,25(OH)(2)D(3) (calcitriol), 25OHD(3), and EB1089 on cell growth and on Vitamin D receptor (VDR) mRNA and 1alpha-hydroxylase (1alpha-OHase) mRNA expression in normal canine prostatic primary cultures. Canine prostatic epithelial cells were isolated, cultured, and treated with vehicle (ethanol), calcitriol, 25OHD(3), and EB1089 at 10(-9) and 10(-7)M. The VDR was present in epithelial and stromal cells of the canine prostate gland.

Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function.

Parathyroid hormone (PTH) is secreted by the chief cells of the parathyroid gland in response to changes in ionized calcium (Ca(2+)) concentrations. In this study, we measured PTH secretion, and PTH mRNA and calcium-sensing receptor (CaR) mRNA expression by equine parathyroid chief cells in vitro. We also evaluated the effects of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha on PTH secretion, and PTH and CaR mRNA expression.

Chronic studies evaluating the carcinogenicity of monomethylarsonic acid in rats and mice.

Monomethylarsonic acid (MMA) was administered in the diet of male and female Fischer F344 rats and B6C3F1 mice in 2-year feeding studies according to US EPA guidelines. Rats were treated with 50, 400, or 1300 ppm MMA and mice were treated with 10, 50, 200, or 400 ppm MMA based on preliminary short-term studies. The highest dose in the male and female rat groups was reduced to 1000 ppm during week 53 and then further reduced to 800 ppm during week 60 due to high mortality in the male rats.

Effect of exogenous human sodium iodide symporter expression on growth of MATLyLu cells.

The sodium iodide symporter (NIS) mediates iodide uptake in thyroid cells and enables the effective radioiodide treatment of thyroid cancers. There is much interest in facilitating radioiodide therapy in other cancers by NIS gene transfer. This study showed that exogenous NIS expression decreased MATLyLu rat prostatic adenocarcinoma cell growth.

Adrenal cortical carcinomas with myxoid differentiation in the domestic ferret (Mustela putorius furo).

A total of 15 adrenocortical carcinomas with myxoid differentiation from 15 ferrets were evaluated in this retrospective study. Six of these ferrets (40%) either were euthanatized or died due to invasive and/or metastatic disease. The myxoid component was a variable part (between 5% and 95%) of the adrenal cortical neoplasm and consisted of sheets and cords of small, polygonal neoplastic cells that formed lumenlike spaces.

Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses.

Abnormalities in calcium (Ca(2+)) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca(2+) regulation in horses. The objectives of the present study were to determine the Ca(2+) set-point in healthy horses, to determine whether the Ca(2+)/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced hypocalcemia or hypercalcemia had an effect on PTH secretion. The Ca(2+) set-point and hysteresis were determined in 12 healthy horses by infusing Na(2)EDTA and calcium gluconate.

Molecular cloning and expression of equine calcitonin, calcitonin gene-related peptide-I, and calcitonin gene-related peptide-II.

In this study, we describe the cloning and tissue expression of equine calcitonin (CT), calcitonin-gene related peptide (CGRP)-I, and CGRP-II cDNA. We also describe a novel divergent form of CGRP (CGRP-I). Equine CT has greatest homology (>85%) to human, rat and mouse subgroups of calcitonins.

Epididymal cribriform hyperplasia with nuclear atypia in p53 homozygous knockout mice on a mixed 129/Sv-FVB/N background.

Epididymal cribriform hyperplasia (ECH) is a variant of normal epididymal histologic features in men, and has also been reported in rats, mice, dogs, cats, and bulls. The epididymal change has been associated with aging, testicular atrophy, cryptorchidism, and germ cell tumors. Epididymal cribriform hyperplasia was observed in p53 homozygous knockout mice on a mixed 129/Sv-FVB/N background, but not in wild-type or heterozygous mice.

Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogues (EB1089 and analog V) on canine adenocarcinoma (CAC-8) in nude mice.

The aim of this study is to determine the effects of 1,25(OH)2D3 and its analogues on tumor growth and body weight, changes in plasma ionized calcium, parathyroid hormone-related protein (PTHrP) production, bone resorption, and the distribution of the 1,25(OH)2D3 receptor (VDR) on tumors in nude mice-bearing the canine adenocarcinoma (CAC-8). Thirty-seven nude mice were implanted subcutaneously with CAC-8. Two weeks after implantation, the mice were divided into 5 groups and injected intraperitoneally 3 times/week for 4 weeks with 5 different substrates.

Cloning and sequencing of the 3'-region of the canine parathyroid hormone-related protein gene and analysis of alternate mRNA splicing in two canine carcinomas.

A canine genomic library in Lambda FIX II vector was screened with a 281-base pair canine PTHrP cDNA to the prepro- and coding regions. Two genomic clones were isolated and mapped to the 3'-end of the PTHrP gene by polymerase chain reaction (PCR) amplification of exons in this region. One clone (3.

Messenger RNA stability of parathyroid hormone-related protein regulated by transforming growth factor-beta1.

Humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome associated with epithelial cancers, including squamous cell carcinoma (SCC), is due to expression and secretion of parathyroid hormone-related protein (PTHrP). Transforming growth factor-beta1 (TGFbeta1), expressed by many tumors, has been demonstrated in vitro to increase the half-life of PTHrP mRNA. In this study, oral squamous carcinoma cells (SCC2/88) had a two-fold increase in PTHrP mRNA stability (from 45 to 90 min) in response to treatment with TGFbeta1.