IFNgamma sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression.

TRAIL preferentially induces apoptosis in tumor cells and virus-infected cells. Unlike other tumor necrosis factor family members, TRAIL does not kill cells from most normal tissues and has thus been proposed as a promising new cancer treatment. Our study demonstrated that IFNgamma combined with TRAIL can trigger apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a minimal effect.

The role of interferon regulatory factor-1 and interferon regulatory factor-2 in IFN-gamma growth inhibition of human breast carcinoma cell lines.

Interferon (IFN) regulatory factor-1 (IRF-1) and IRF-2 play opposing roles in the regulation of many IFN-gamma-inducible genes. To investigate the signal transduction pathway in response to IFN-gamma in light of differences in growth effects, we selected four human breast carcinoma cell lines based on a spectrum of growth inhibition by IFN-gamma. MDA468 growth was markedly inhibited by IFN-gamma, and it showed substantial induction of IRF-1 mRNA but little IRF-2 induction.

Non-bronchoscopic sampling and culture of bronchial epithelial cells in children.

Background: The bronchial epithelium is likely to play a vital role in airway diseases in children, such as asthma and viral-associated wheeze. In adults, studies with primary bronchial epithelial cells cultured from samples obtained by fibre-optic bronchoscopy have provided key insights into the role of the epithelial cell. However, it is difficult to justify bronchoscopy in children to obtain epithelial cells for research purposes.

Multiple endocrine neoplasia type 1: duodenopancreatic tumors.

Duodenopancreatic endocrine tumors are the most frequently lethal part of MEN-1. The management of these patients is complicated by the variable hormonal function of the tumors, and the often indolent but occasionally lethal nature of the tumors. This article reviews our current approach to the diagnosis, surveillance and management of these patients.

Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1.

Background: Patients with multiple endocrine neoplasia (MEN) type 1 risk premature death from pancreatic endocrine tumours (PETs). Endoscopic ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A screening and therapeutic approach for asymptomatic patients is delineated in which EUS plays a pivotal role.

Multiple endocrine neoplasia type 1: duodenopancreatic tumours.

The pancreaticoduodenal disease in Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of death due to the syndrome, and the most controversial with regard to its management. This article discusses the current data and recommendations with respect to disease screening, functional tumour diagnosis, natural history, preoperative imaging, operative strategy and follow-up.

N-isonicotinoyl-(L)-4-aminophenylalanine derivatives as tight binding VLA-4 antagonists.

A series of isonicotinoyl-(L)-aminophenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. These compounds exhibit subnanomolar binding affinity to VLA-4 and significant off-rates. The interplay between off-rate, protein binding and pharmacokinetics is discussed.

A small molecule very late antigen-4 antagonist can inhibit ovalbumin-induced lung inflammation.

A nonpeptidyl small molecule antagonist, compound A, to nonactivated very late antigen-4 (VLA4) was examined in lung inflammation induced by a single dose of ovalbumin challenge. Compound A presented a good pharmacokinetic property, when given intratracheally, and the blood cells from such pharmacokinetic study showed good receptor occupancy of the compound for approximately 8 hours. Compound A was then tested in an ovalbumin-induced airway inflammation model by intranasal or intravenous route of administration.

Identification of HLA-A3-restricted CD8+ T cell epitopes derived from mammaglobin-A, a tumor-associated antigen of human breast cancer.

Mammaglobin-A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and metastatic breast tumors. Thus, mammaglobin-A-specific T cell immune responses may provide an important approach for the design of breast cancer-specific immunotherapy.

Recurrent or persistent hyperparathyroidism.

Approximately 90% of patients with primary hyperparathyroidism (PHPT) are cured by parathyroidectomy at the initial neck exploration. Those not cured either remain hypercalcemic in the immediate postoperative period or develop hypercalcemia after a long period of normocalcemia. Almost all cases of hypercalcemia after neck exploration for PHPT are evident early in the postoperative period and are caused either by an overlooked parathyroid adenoma or an incomplete resection of hyperplastic parathyroid tissue.

Childhood and adolescent thyroid carcinoma.

Objectives: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma.

Methods: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years.

Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma.

Regulatory T cells (T(reg)) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. In mice, depletion of T(reg) by Ab therapy leads to more efficient tumor rejection. T(reg)-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer.

Papillary thyroid cancer.

Papillary thyroid cancer is the most common neoplasm of the thyroid gland. Surgical resection is the cornerstone of therapy. There is controversy regarding the extent of resection, ranging from thyroid lobectomy plus isthmusectomy to total thyroidectomy, but in experienced hands total thyroidectomy has many significant advantages over a lesser operation.

Substituted tetrahydrofuroyl-1-phenylalanine derivatives as potent and specific VLA-4 antagonists.

A series of substituted tetrahydrofuroyl-1-phenylalanine derivatives was prepared and evaluated as VLA-4 antagonists. Substitution of the alpha carbon of the tetrahydrofuran with aryl groups increased the specificity for VLA-4 versus alpha(4)beta(7) while amide substitution increased the potency of the series without increasing the specificity. Substitution of the beta carbon of the tetrahydrofuran with keto or amino groups slightly improved the specificity for VLA-4 versus alpha(4)beta(7) but with a significant loss in binding affinity for VLA-4.

N-Tetrahydrofuroyl-(L)-phenylalanine derivatives as potent VLA-4 antagonists.

Given the proposed involvement of VLA-4 in inflammatory processes, a program to identify orally active VLA-4 antagonists was initiated. Herein, we report the discovery of a N-tetrahydrofuroyl-(L)-phenylalanine derivative (17) and related analogues as potent VLA-4 antagonists with good oral bioavailability.

Adrenalectomy for familial pheochromocytoma in the laparoscopic era.

Objective: To report the results of treatment of patients with familial pheochromocytomas in the laparoscopic era.

Summary Background Data: The optimal surgical management of pheochromocytomas that arise in familial neoplasia syndromes may be complicated by bilateral involvement and associated endocrinopathies.

Methods: Twenty-one patients with familial pheochromocytomas (15 with multiple endocrine neoplasia [MEN] 2A, 4 with MEN 2B, 1 each with von Hippel-Lindau and neurofibromatosis type 1) underwent adrenalectomy between December 1993 and July 2001.

Gastrointestinal manifestations of multiple endocrine neoplasia type 2.

Objective: To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes.

Summary Background Data: The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems.

The resistance of P. acnes--primed interferon gamma-deficient mice to low-dose lipopolysaccharide-induced acute liver injury.

Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure. Although interferon gamma (IFN-gamma) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response. To examine the role of IFN-gamma in lipopolysaccharide (LPS)-induced injury, we administered LPS (20 or 800 microg/mouse) alone or as low-dose LPS (20 microg/mouse) 7 days after heat-killed Propionibacterium acnes (P.

N-aryl 2,6-dimethoxybiphenylalanine analogues as VLA-4 antagonists.

A series of N-arylated phenylalanine derivatives has been synthesized and has been shown to be potent inhibitors of the integrin VLA-4. N-phenyl and N-heteroaryl derivatives with hydrogen bond acceptors in the meta position demonstrated low nanomolar activity against VLA-4.

Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose-positron emission tomography.

Background: Thyroid tumors often exhibit increased metabolic activity, as evidenced by enhanced glucose uptake on positron emission tomography (PET) with use of (18)F-fluorodeoxyglucose (FDG). The incidence of new thyroid lesions found on routine FDG-PET has not been previously reported.

Methods: A retrospective review of all patients who underwent FDG-PET imaging at our institution from June 1, 1996, through March 15, 2001, identified patients with a newly diagnosed thyroid lesion.

Outcomes analysis in patients undergoing laparoscopic adrenalectomy for hormonally active adrenal tumors.

Background: Laparoscopic adrenalectomy (LA) has become the preferred method of removal of most adrenal neoplasms, but few studies have evaluated the functional outcomes of this approach. The purpose of this study was to analyze our operative results and the clinical and biochemical responses to LA in patients with various hormonally active adrenal tumors.

Methods: From 1993 through November 2000, 72 patients with functional adrenal tumors underwent attempted LA.

Evaluation of the performance and clinical impact of a rapid intraoperative parathyroid hormone assay in conjunction with preoperative imaging and concise parathyroidectomy.

Background: (99m)Tc-sestamibi scans and rapid, intraoperative intact parathyroid hormone (PTH) assays allow preoperative identification of diseased glands and intraoperative confirmation of diseased gland removal, respectively. Use of these two new technologies may facilitate simpler, more concise surgery, shorter hospital stays, and decreased costs for frozen-section analysis. One major drawback to this new strategy has been the high cost of rapid point-of-care PTH assays.

Interferon regulatory factor expression in human breast cancer.

Objective: To investigate the expression of interferon regulatory factors 1 and 2 (IRF-1 and IRF-2) in human breast cancer.

Summary Background Data: Interferon regulatory factors 1 and 2 are transcription factors in the interferon gamma signal transduction pathway. IRF-1 acts as the effector arm of the interferon gamma response; IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity.

Factors influencing the induction of DT-diaphorase activity by 1,2-dithiole-3-thione in human tumor cell lines.

NAD(P)H:(quinone acceptor)oxidoreductase (DT-diaphorase) is a two-electron reducing enzyme that activates bioreductive antitumor agents and is induced by a wide variety of compounds including 1,2-dithiole-3-thione (D3T). We investigated factors influencing DT-diaphorase induction in fourteen human tumor cell lines. Four cell lines had basal DT-diaphorase activity that was increased by D3T treatment (group A), six cell lines had basal DT-diaphorase activity but the activity was not increased by D3T (group B), and four cell lines had low enzyme activity without, or with, D3T (group C).