Human pollution exposure correlates with accelerated ultrastructural degradation of hair fibers.

Exposure to pollution is a known risk factor for human health. While correlative studies between exposure to pollutants such as polycyclic aromatic hydrocarbons (PAHs) and human health exist, and while in vitro studies help to establish a causative connection, in vivo comparisons of exposed and nonexposed human tissue are scarce. Here, we use human hair as a model matrix to study the correlation of PAH pollution with microstructural changes over time.

Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy.

Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM-151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study.A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients.

Phase I and pharmacokinetic study of bortezomib in combination with idarubicin and cytarabine in patients with acute myelogenous leukemia.

Purpose: Proteasome inhibition results in cytotoxicity to the leukemia stem cell in vitro. We conducted this phase I study to determine if the proteasome inhibitor bortezomib could be safely added to induction chemotherapy in patients with acute myelogenous leukemia (AML).

Experimental Design: Bortezomib was given on days 1, 4, 8, and 11 at doses of 0.

Bortezomib therapy in patients with relapsed or refractory lymphoma: potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity.

Purpose: To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures.

Patients And Methods: Patients received bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of a 3-week cycle.

Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma.

Background: Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma.

Methods: Bortezomib 1.0 or 1.

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies.

Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.

Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL).

Patients And Methods: Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

Purpose: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Patients And Methods: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.

Promising activity of the proteasome inhibitor bortezomib (VELCADE) in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma: ASH poster session 517-II.

Dr. O'Connor delivered the following material as a poster at the 2003 American Society of Hematology meeting highlighting results from his work with bortezomib in the treatment of non-Hodgkin's and mantle cell lymphoma. A full publication of his results will appear later this year.

A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor.

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v.

Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma.

Purpose: A randomized, double-blind, placebo-controlled trial was performed to compare the toxicity and biologic effects of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus the recombinant human soluble p75 tumor necrosis factor (TNF) receptor immunoglobulin G (IgG) chimera (rhuTNFR:Fc) with high-dose IL-2 alone in patients with advanced melanoma and renal cell carcinoma.

Patients And Methods: Twenty patients with advanced melanoma or renal cell carcinoma were randomized to receive IL-2 (Chiron, Emeryville, CA) 600,000 IU/kg every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) combined with placebo or the rhuTNFR:Fc fusion protein (Immunex, Seattle, WA) 10 mg/m2 on days 1 and 15 and 5 mg/m2 on days 3, 5, 17, and 19. The impact of rhuTNFR:Fc on IL-2 toxicity and biologic effects was evaluated.

Phase I trial of interleukin 2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera.

Our purpose was to determine the effective biological dose and/or maximum tolerated dose of recombinant human tumor necrosis factor receptor:IgG chimera (rhuTNFR:Fc; Immunex, Seattle, WA) in combination with interleukin 2 (IL-2) with regard to reduction in IL-2 toxicity and modulation of biological effects of high-dose IL-2 administration. Twenty-four patients with metastatic cancer were treated with escalating doses of rhuTNFR:Fc at 1, 1, 5, 10, and 20 mg/m2 i.v.

Induction of circulating antagonists to IL-1 and TNF by IL-2 administration and their effects on IL-2 induced cytokine production in vitro.

The objectives of this study were to determine whether intensive immunotherapy with IL-2 results in detectable levels of circulating IL-1 and TNF antagonists and whether the levels achieved in vivo are sufficient to affect the generation of secondary proinflammatory cytokines such as IL-1 beta and TNF-alpha. We also sought to determine the extent to which endogenous TNF mediates the generation of an IL-1 antagonist by IL-2-activated PBMCs. In patients undergoing high dose IL-2 immunotherapy, plasma IL-1 receptor antagonist (IL-1ra) levels rose dramatically after the first IL-2 injection, reaching a plateau of 11.

Induction of circulating soluble tumour necrosis factor receptor and interleukin 1 receptor antagonist following interleukin 1 alpha infusion in humans.

The aim of this study was to investigate circulating levels of tumour necrosis factor soluble receptor p55 (TNFsrp55) and interleukin 1 receptor antagonist (IL-1ra) in cancer patients undergoing treatment with IL-1 alpha. Patients were treated with 0.03 micrograms/kg IL-1 alpha administered intravenously over a 30 min interval daily for five consecutive days.

Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.

The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma samples were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous (IV) infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55 (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs).

Possible myocardial toxicity associated with interleukin-4 therapy.

Interleukin (IL)-4 is a cytokine produced by T lymphocytes, which may play a role in allergic inflammatory processes through its stimulatory effects on immunoglobulin E production and mast cells. In this report, we describe a patient with metastatic melanoma involving the heart who had biopsy-proven myocarditis after treatment with high-dose IL-4. Because of the uncharacteristic predominance of polymorphonuclear and mast cells in the inflammatory infiltrate of this patient's myocardium, we postulate a unique mechanism of IL-4-associated myocarditis.

A method for the detection of erythrocyte-bound interleukin-8 in humans during interleukin-1 immunotherapy.

Interleukin-8 (IL-8) has been recently shown to bind to human erythrocytes with high affinity and is therefore potentially difficult to detect in serum or plasma. IL-8 is transiently elevated in the serum of baboons after the administration of interleukin-1 alpha (IL-1 alpha). The objective of this study was to investigate whether IL-8 can be detected in the plasma or in detergent-lysed erythrocytes from cancer patients undergoing treatment with IL-1 alpha.

Suppression of IL-2-induced SAA gene expression in mice by the administration of an IL-1 receptor antagonist.

The hepatic acute phase response induced by the administration of interleukin (IL)-2 is most likely mediated by secondary cytokines. In this investigation, we examined the role of endogenous IL-1 in the synthesis of the hepatic acute phase protein serum amyloid A (SAA) during IL-2 treatment. The injection of IL-2 induced SAA gene expression in the liver.

Cost of screening for colorectal cancer: results of a community mass screening program and review of the literature.

Colorectal cancer is the second most common form of cancer in the United States, but controversy exists over the feasibility, benefits, and methods of screening. We conducted a large-scale, community-based screening program to determine the cost of screening for colorectal cancer. Based on detailed cost analysis, we arrived at a cost of $15,233 per case of colon cancer diagnosed through mass screening, and $7611 per polyp discovered.