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3.  Comparison of Radiosensitizing Effects of the mTOR Inhibitor CCI-779 to Cisplatin in Experimental Models of Head and Neck Squamous Cell Carcinoma 
Molecular cancer therapeutics  2009;8(8):2255-2265.
Purpose
To determine if the mTOR inhibitor CCI-779 can sensitize head and neck squamous cell carcinoma (HNSCC) to radiotherapy (XRT) and compare the radiosensitizing effects to cisplatin with its known considerable toxicity.
Experimental Design
Radiosensitizing effects of CCI-779 were assayed on HNSCC cell lines in vitro. CCI-779 (5mg/kg), cisplatin (1 mg/kg) and XRT (2 Gy) alone and in combination were evaluated for antitumor activity in mice bearing FaDu and SCC40 xenografts. Effects of CCI-779 on radiation-induced activation of the Akt/mTOR pathway were analyzed.
Results
Although CCI-779 did not sensitize HNSCC cells to ionizing radiation in vitro, combination of CCI-779 and XRT significantly augmented the in vivo tumor growth inhibitory effects of XRT and CCI-779 (P<0.05). In addition CCI-779+XRT suppressed tumor growth more effectively than cisplatin+XRT (P<0.05). CCI-779+XRT significantly improved survival compared to XRT alone in both cisplatin-sensitive FaDu (P<0.01) and cisplatin-resistant SCC40 xenograft mice (P<0.05). There were no additional benefits of adding cisplatin to CCI-779+XRT. CCI-779 significantly attenuated irradiation-induced upregulation of the mTOR pathway, increased apoptosis and displayed potent antiangiogenic activity in FaDu xenografts that was further enhanced by its combination with radiotherapy (P<0.05) which may explain the mechanism of its selective radiosensitizing effects in vivo and not in vitro.
Conclusions
Antitumor activity of radiotherapy was enhanced when combined with CCI-779 in HNSCC xenograft model. CCI-779+XRT showed antitumor activity superior to conventional chemoradiotherapy with cisplatin. These results pave the way for clinical trials utilizing molecular targeted therapy with CCI-779 in combination with radiotherapy for HNSCC treatment.
doi:10.1158/1535-7163.MCT-08-1184
PMCID: PMC2758817  PMID: 19625495
rapamycin analogues; temsirolimus; mTOR; in vivo; apoptosis
4.  Primary Intracranial Leiomyosarcoma: Report of a Case and Review of the Literature 
Sarcoma  2006;2006:52140.
A 26-year old man presented with a 3-month history of a progressively enlarging palpable parieto-occipital mass. A CT scan indicated the lesion arose from the dura with bony destruction. A stealth assisted craniotomy was performed with the provisional diagnosis of osteoblastic meningioma. Further histopathologic analysis of the intracranial mass was consistent with leiomyosarcoma. Staging evaluation, including CT and PET scans, demonstrated no other sites of disease. Despite complete surgical resection and radiotherapy to the resection site, the disease recurred locally and systematically 5 months later. Primary intracranial mesenchymal tumors are rare and few cases have been previously reported. Outcomes have been universally poor and current therapeutic approaches appear to have only limited benefit.
doi:10.1155/SRCM/2006/52140
PMCID: PMC1779506  PMID: 17496995

Results 1-4 (4)