Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma

Deregulated expression of inhibitors of apoptosis (programmed cell death) may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to therapy. In this study, we investigated the potential expression and prognostic significance of the apoptosis inhibitor survivin in squamous cell carcinoma (SCC). A series of 135 cases of SCC including 46 oral SCC and 89 cutaneous SCC was analyzed for survivin expression by immunohistochemistry and Western blotting. Survivin was found in 57 cases (64%) of skin SCC and 26 cases (56%) of oral SCC, with weighted survivin scores ranging from 1 to 12. In contrast, normal oral epithelium, normal skin epithelium, and skin annexa did not express survivin. Survivin expression significantly (P 1.5 cm and invariably associated with lymph node metastasis. These data suggest that survivin expression may predictively identify cases of SCC with more aggressive and invasive clinical phenotype, potentially warranting closer follow-up protocols

Proteomic profiling of PrP27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders characterized by the accumulation in the CNS of a pathological conformer (PrPTSE) of the host-encoded cellular prion protein (PrPC). PrPTSE has a central role in the pathogenesis of the disease but other factors are likely involved in the pathological process. In this work we employed a multi-step proteomic approach for the identification of proteins that co-purify with the protease-resistant core of PrPTSE (PrP27-30) extracted from brains of hamsters with experimental scrapie. We identified ferritin, calcium/calmodulin-dependent protein kinase a type II, apolipoprotein E, and tubulin as the major components associated with PrP27-30 but also trace amounts of actin, cofilin, Hsp90a, the g subunit of the T-complex protein 1, glyceraldehyde 3-phosphate dehydrogenase, histones, and keratins. Whereas some of these proteins (tubulin and ferritin) are known to bind PrP, other proteins (calcium/calmodulin-dependent protein kinase a type II, Hsp90a) may associate with PrPTSE fibrils during disease. Apolipoprotein E and actin have been previously observed in association with PrPTSE, whereas cofilin and actin were shown to form abnormal rods in the brain of patients with Alzheimer disease. The roles of these proteins in the development of brain lesions are still unclear and further work is needed to explain their involvement in the pathogenesis of TSEs

Volumetric intensity modulated arc therapy for stereotactic body radiosurgery in oligometastatic breast and gynecological cancers: Feasibility and clinical results

In the present study, the preliminary results of the first stereotactic body radiosurgery (SRS) experience with volumetric intensity modulated arc therapy (VMAT) in oligometastatic breast and recurrent gynecological tumors (OBRGT) are reported in terms of feasibility, toxicity and efficacy. Patients were treated in a head-first supine treatment position on a customized body frame immobilization shell. SRS-VMAT treatment plans were optimized using the ERGO++ treatment planning system. Response assessment was performed 8-12 weeks after treatment by morphologic imaging modalities, or if feasible, also by functional imaging. Thirty-six lesions in 24 consecutive patients (median age, 63 years; range, 40-81) were treated: 13.9% had primary or metastatic lung lesions, 30.5% had liver metastases, 36.1% had bone lesions, 16.7% had lymph node metastases and 2.8% had a primary vulvar melanoma. The median dose was 18 Gy (BED2 Gy, \u3b1/\u3b2: 10=50.4 Gy), the minimal dose was 12 Gy (BED2 Gy, \u3b1/\u3b2: 10=26.4 Gy) and the maximal dose was 28 Gy (BED2 Gy, \u3b1/\u3b2: 10=106.4 Gy). Seven patients (29.2%) experienced acute toxicity, which however was grade 2 in only 1 case. Moreover, only 3 patients (12.5%) developed late toxicity of which only 1 was grade 2. Objective response rate was 77.7% including 16 lesions achieving complete response (44.4%) and 12 lesions achieving partial response (33.3%). The median duration of follow-up was 15.5 months (range, 6-50). Recurrence/progression within the SRS-VMAT treated field was observed in 6 patients (total lesions=7) with a 2-year inside SRS-VMAT field disease control expressed on a per lesion basis of 69%. Recurrence/progression of disease outside the SRS-VMAT field was documented in 15 patients; the 2-year outside SRS-VMAT field metastasis\u2011free survival, expressed on a per patient basis, was 35%. Death due to disease was documented in 6 patients and the 2-year overall survival was 58%. Although the maximum tolerated dose was not reached, SRS-VMAT resulted in positive early clinical results in terms of tumor response, local control rate and toxicity