Cerebellar glioblastoma: a retrospective review of 21 patients at a single institution.

Primary cerebellar glioblastoma (CGB) comprises only 0.4-3.4% of all intracranial glioblastoma.

Accelerated disease progression in prostate cancer and bone metastases with platelet-derived growth factor receptor inhibition: observations with tandutinib.

Background: Activated platelet-derived growth factor receptor (p-PDGFR) is frequently expressed in bone metastases of castration-resistant prostate cancer (CRPC). Phase II study of tandutinib was conducted to assess the effects of a continuously administered highly potent PDGFR inhibitor in this disease state.

Methods: Men with progressive CRPC, bone metastases, and prior taxane chemotherapy were treated with oral tandutinib 500 mg twice daily until disease progression under a two-stage design with the 8-week freedom-from-progression (FFP) rate as the primary endpoint.

Proteasome enzymatic activities in plasma as risk stratification of patients with acute myeloid leukemia and advanced-stage myelodysplastic syndrome.

Purpose: Cytogenetic abnormalities are currently the most important predictors of response and clinical outcome for patients with acute myeloid leukemia (AML) or advanced-stage myelodysplastic syndrome (MDS). Because clinical outcomes vary markedly within cytogenetic subgroups, additional biological markers are needed for risk stratification.

Experimental Design: We assessed the utility of measuring pretreatment proteasome chymotrypsin-like, caspase-like, and trypsin-like activities in plasma to predict response and survival of patients with AML (n = 174) or advanced-stage MDS (n = 52).

Number of metastatic sites is a strong predictor of survival in patients with nonsmall cell lung cancer with or without brain metastases.

Background: The staging system for non-small cell lung cancer (NSCLC) does not consider tumor burden or number of metastatic sites, although oligometastases are more favorable.

Methods: Using log-rank testing, the authors analyzed overall survival (OS) in 1284 patients newly presenting with metastatic NSCLC by number of metastatic organ sites and the presence of brain metastases.

Results: OS for patients without brain metastases was found to be correlated with the number of metastatic sites (P = .

KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.

Purpose: EGFR gene mutations and increased EGFR copy number have been associated with favorable response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in patients with non-small-cell lung cancer (NSCLC). In contrast, KRAS mutation has been shown to predict poor response to such therapy. We tested the utility of combinations of these three markers in predicting response and survival in patients with NSCLC treated with EGFR-TKIs.

Cost-effectiveness of influenza vaccination in working-age cancer patients.

Background: Despite recommendations to immunize all patients at an increased risk of influenza complications, the vaccine utilization among high-risk nonelderly adults remains low and its cost-effectiveness is unclear. In the current study, the authors analyzed the cost-effectiveness of influenza vaccination in working-age (ages 20-64 years) cancer patients.

Methods: The authors developed a decision-analytic model, from the societal perspective, using epidemiologic, vaccine effectiveness, resource utilization, cost, survival, and utility data from published sources, supplemented with data collected from the authors' own institutional accounting system.

mda-7 In combination with bevacizumab treatment produces a synergistic and complete inhibitory effect on lung tumor xenograft.

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has shown antitumor activity by inhibiting tumor angiogenesis in preclinical and clinical studies. However, bevacizumab monotherapy does not induce complete tumor regression. Therefore, additional treatments must be combined with bevacizumab to promote tumor regression.

Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate cancer.

Background: This is a phase I/II trial of thalidomide with estramustine and paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent previous chemotherapy.

Patients And Methods: Men with progressive AIPC were treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140 mg 3 times daily on days 1-5 and days 8-12) every 21 days.

Results: Phase I: first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the designated maximum tolerated dose).

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer.

We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine protein kinase, as a new molecular target for treating anaplastic thyroid cancer. ILK mediates cell growth and survival signals and is overexpressed in a number of cancers. Therefore, we hypothesized that inhibition of ILK leads to growth arrest and apoptosis of thyroid cancer cells.

Epidemiology and outcomes of serious influenza-related infections in the cancer population.

Background: Although patients with cancer generally respond favorably to vaccination, they may not receive annual influenza vaccinations. The current population-based study described the epidemiology and outcomes of potentially preventable, serious influenza-related infections in patients with cancer.

Methods: From the Nationwide Inpatient Sample, the authors created a subsample that included discharges with any International Classification of Diseases, ninth revision, diagnosis code for cancer and principal diagnosis code for influenza, bronchopneumonia, or pneumonia caused by an unspecified organism.

Antivascular therapy of human follicular thyroid cancer experimental bone metastasis by blockade of epidermal growth factor receptor and vascular growth factor receptor phosphorylation.

Patients suffering from bone metastases of follicular thyroid carcinoma (FTC) have a poor prognosis because of the lack of effective treatment strategies. The overexpression of epidermal growth factor receptor (EGFR) associated with increased vascularity has been implicated in the pathogenesis of FTC and subsequent bone metastases. We hypothesized that inhibiting the phosphorylation of the EGFR and vascular endothelial growth factor receptor (VEGFR) by AEE788, a dual tyrosine kinase inhibitor of EGFR and VEGFR, in combination with paclitaxel would inhibit experimental FTC bone lesions and preserve bone structure.

AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice.

Purpose: We investigated whether concomitant blockade of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways by AEE788, a dual inhibitor of EGFR and VEGFR tyrosine kinases, would inhibit the growth of cutaneous squamous cell carcinoma (SCC) cells and human cutaneous cancer xenografts in nude mice.

Experimental Design: We examined the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in cutaneous SCC cells expressing EGFR and VEGFR-2 and cutaneous SCC cell growth and apoptosis. We assessed the in vivo antitumor effects of AEE788 in a xenograft model in nude mice.

An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice.

Purpose: To develop an orthotopic model of anaplastic thyroid carcinoma (ATC) in athymic nude mice.

Experimental Design: Various thyroid carcinoma cell lines were injected into the thyroid gland of athymic nude mice to determine whether such injection was technically feasible. ATC cells were then injected into the thyroid gland or the subcutis of nude mice at various concentrations, and the mice were then followed for tumor development.

Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer.

Purpose: No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy.

Experimental Design: The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC.

Comparison of molecular abnormalities in bronchial brushings and tumor touch preparations.

Background: Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC).

Methods: Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed.

Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents.

Background: High concentrations of interferon beta (IFN-beta) inhibit malignant cell growth in vitro. However, the therapeutic utility of IFN-beta in vivo is limited by its excessive toxicity when administered systemically at high doses. Mesenchymal stem cells (MSC) can be used to target delivery of agents to tumor cells.

Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade.

Expression of the epidermal growth factor (EGF) and activation of its receptor (EGFR), a tyrosine kinase, are associated with progressive growth of head and neck cancer. Expression of the vascular endothelial growth factor (VEGF) is associated with angiogenesis and progressive growth of tumor. The tyrosine kinase inhibitor NVP-AEE788 (AEE788) blocks the EGF and VEGF signaling pathways.

Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo.

Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy.