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Anthony Brade

Publications and source records attributed to Anthony Brade.

3 recordsLinked to original sources
PubMed2006

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study.

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.

Adult↗
PubMed2004

Kinase-dead PKB gene therapy combined with hyperthermia for human breast cancer.

We have previously demonstrated that protein kinase B (PKB) is a mediator of heat-induced apoptosis for human breast cancer cells. To investigate the therapeutic potential of abrogating the function of this important survival protein, a novel replication-deficient adenovirus was constructed, wherein a mutant, kinase-inactive PKB gene (AAA) was inserted downstream of the CMV promoter. Two human breast cancer cell lines, MCF-7 and MDA-468, were treated, along with the MCF-10 serving as a "normal" mammary epithelial comparator. Apoptosis was increased with adv.AAA (25 PFU/cell) infection alone, but was significantly enhanced with the addition of heat exposure. Differential survival was observed with the MDA-468 cancer cells being more sensitive than the MCF-7 cells. The MCF-10 cells, in contrast, were most resistant to these treatments. Results from the clonogenic assay reflected the apoptosis data, with an apparent additive interaction between adv.AAA and hyperthermia treatments, again with greater differential sensitivity of the malignant, compared to the "normal" mammary epithelial cells. Heat or adv.beta-gal treatments led to phosphorylation of PKB and Forkhead, but this phosphorylation was reduced with adv.AAA therapy. In parallel, the combination of adv.AAA and heat treatment reduced PKB kinase activity more so than with either heat or adv.beta-gal alone. In conclusion, our results demonstrate that inhibition of the PKB-dependent survival pathway will promote apoptosis and thermosensitization in malignant breast cancer cells, with relative sparing of their normal counterpart, suggesting that a therapeutic gain could be achievable using this therapeutic strategy.

Adenoviridae↗