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PURPOSE To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of(More)
PURPOSE To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group(More)
HER2 is a ligand-less tyrosine kinase receptor of the ErbB family that is frequently overexpressed in breast cancer. It undergoes proteolytic cleavage that results in the release of the extracellular domain and the production of a truncated membrane-bound fragment, p95. We show that HER2 shedding is activated by 4-aminophenylmercuric acetate (APMA), a(More)
PURPOSE To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy. PATIENTS AND METHODS Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until(More)
The factors and mechanisms that transduce the intracellular signals sent upon activation of the receptor for the epidermal growth factor (EGFR) and related receptors are reasonably well understood and, in fact, are the targets of anti-tumor drugs. In contrast, less is known about the mechanisms implicated in sending the signals that activate these(More)
BACKGROUND New chemotherapeutic agents, including paclitaxel and gemcitabine, are active in advanced bladder carcinoma, and combination regimens with these agents have shown promising results. Unlike conventional chemotherapy regimens, such as methotrexate, vinblastine, doxorubicin, and cisplatin, there are no data available on key predictive factors for(More)
PURPOSE The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical(More)
Low levels of telomerase activity have recently been detected in human primitive hematopoietic cells, however, blood cells exhibit telomere shortening on cell proliferation. This challenging observation led us to study telomerase regulation and telomere length in human hematopoietic progenitor cells from fetal liver (FL), cord blood (CB), peripheral blood(More)
Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a(More)
BACKGROUND This study examined the impact of the Recurrence Score (RS) in Spanish breast cancer patients and explored the associations between clinicopathological markers and likelihood of change in treatment recommendations. PATIENTS AND METHODS Enrollment was offered consecutively to eligible women with estrogen receptor-positive; human epidermal growth(More)