Deregulation of MADS-box transcription factor genes in a mutant defective in the WUSCHEL-LIKE HOMEOBOX gene EVERGREEN of Petunia hybrida.

Angiosperm inflorescences develop in two fundamentally different ways. In monopodial plants, for example in Arabidopsis thaliana, the flowers are initiated as lateral appendages of a central indeterminate inflorescence meristem. In sympodial plants, flowers arise by terminal differentiation of the inflorescence meristem, while further inflorescence development proceeds from new sympodial meristems that are generated at the flank of the terminal flower. We have used the sympodial model species Petunia hybrida to investigate inflorescence development. Here, we describe a mutant, bonsai (bns), which is defective in flower formation, inflorescence branching, and control of meristem size. Detailed microscopic analysis revealed that bns meristems retain vegetative charateristics including spiral phyllotaxis. Consistent with a block in flower formation, bns mutants exhibit a deregulated expression of various MADS-box genes. Molecular analysis revealed that the bns mutant carries a transposon insertion in the previously described EVERGREEN (EVG) gene, which belongs to the WUSCHEL-LIKE HOMEOBOX (WOX) transcription factor gene family. EVG falls in the WOX9 subfamily, which has diverse developmental functions in angiosperms. The comparison of WOX9 orthologues in five model species for flowering shows that these genes play functionally divergent roles in monopodial and sympodial plants, indicating that the WOX9 regulatory node may have played an important role in the evolution of shoot architecture.

Breast cancer electron intraoperative radiotherapy: assessment of preoperative selection factors from a retrospective analysis of 758 patients and review of literature.

PURPOSE: To report our experience with full-dose 21 Gy IORT in early breast cancer patients after breast-conserving surgery to define most important selection factors. METHODS: Seven hundred and fifty eight patients, subjected to conserving surgery and IORT, were retrospectively analyzed evaluating most important clinical outcomes. RESULTS: Median follow up was 5.2 years. Results from Cox analyses defined 2 groups of patients, "suitable" (age > 50 years, non lobular histology, tumour size ≤ 2 cm, pN0 or pNmic, ki67 ≤ 20%, non triple negative receptor status and G1-G2) and "unsuitable" for IORT, with a higher rate of breast related events moving from "suitable" to "unsuitable" group. The 5 year rate of IBR is 1.8% in suitable group with significant differences versus unsuitable (1.8 vs. 11.6%, p < 0.005). Same differences between two groups were evidenced in true local relapse (0.6 vs. 6.9%, p < 0.005) and in new ipsilateral BC (1.1 vs. 4.7%, p < 0.015). CONCLUSIONS: In our current practice we consider the following preoperative factors to select patients suitable for IORT: age > 50 years, absence of lobular histology, tumor size ≤ 2 cm, pN0 or pNmic, according to APBI consensus statement, including also ki67 ≤ 20%, non triple negative receptor status and G1-G2.

Acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with concurrent cetuximab and radiotherapy.

PURPOSE: The authors report acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with radiotherapy and cetuximab. MATERIALS AND METHODS: Data collection was performed prospectively on patients treated from September 2007 to March 2009. Treatment consisted of 64.8-70 Gy radiotherapy in conventional fractions and cetuximab. RESULTS: Two out of 14 patients did not complete the planned combined treatment; radiotherapy was temporarily suspended in six other patients. Seven of 12 patients received cetuximab until the end of radiotherapy. Treatment breaks were principally due to severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients and G3-4 mucous toxicity in seven (50%). One patient died of sepsis. CONCLUSIONS: In our experience, severe acute toxic reactions are common in patients treated with radiotherapy and concurrent cetuximab, resulting in frequent breaks or incomplete treatment with potential reduction in disease control.

Stereotactic radiosurgery plus whole-brain radiotherapy for treatment of multiple metastases from non-small cell lung cancer.

BACKGROUND: The aim of this study was to evaluate local control and survival rates after stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) for the treatment of multiple brain metastases from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2004 and September 2008, sixty-six patients with multiple brain metastases from NSCLC were enrolled in this prospective study. All patients were required to have 2-3 brain metastases and Karnofsky performance status (KPS) > or = 70. WBRT treatment dose was 30 Gy in 10 fractions followed by SRS. A matched control population treated with WBRT alone to a dose of 30 Gy in 10 fractions was used for comparison. RESULTS: The median survival was 10.3 months in the WBRT plus SRS group and 7.2 months in the WBRT group (p=0.005). The 6-month and 12-month survival rates were 90% and 38% in the SRS plus WBRT group and 84% and 19% in the WBRT group (p=0.01). Stable extracranial disease and KPS were significant predictive factors of survival in both groups (p=0.001). Death due to neurological causes occurred in 18% and 35% of patients treated with WBRT plus SRS and WBRT (p=0.02), respectively. Disease control in the brain was 10 months in the SRS plus WBRT group and 7 months in the WBRT group (p=0.001); the 6-month and 12-month control rates were 82% and 42% for WBRT plus SRS, and 75% and 18% for WBRT (p=0.001), respectively. The 6-month and 12-month control rates of treated lesions (local control) were 90% and 47% in the WBRT group, and 100% and 93% in the WBRT plus SRS group (p=0.001). CONCLUSION: WBRT plus SRS is a safe, minimally invasive and well-tolerated treatment for patients with up to three brain metastases from NSCLC. The treatment is associated with longer survival and better disease control in comparison with WBRT alone. Survival benefits need to be confirmed by large randomized studies.

Chemotherapy for glioblastoma: current treatment and future perspectives for cytotoxic and targeted agents.

Glioblastoma is the most frequent and devastating primary malignant brain tumor in adults. Surgery followed by standard radiotherapy with concomitant and adjuvant chemotherapy with temozolomide is the standard of care in patients with glioblastoma, however the prognosis remains poor with a median survival in the range of 12-15 months. Common genetic abnormalities in glioblastoma are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy. Special attention has been focused on targets such as epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and on pathways such as the phosphatidylinositol-3kinase/Akt/mammalian target of rapamycin and Ras/Raf/mitogen-activated protein-kinase pathways. Several signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials, including antiangiogenic agents (bevacizumab, enzastaurin), and inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib), mammalian target of rapamycin (temsirolimus, everolimus) and integrin (cilengitide). Although preliminary clinical results of the use of targeted agents have not translated into significantly better survival, more recent phase II trials are exploring the combination of multitargeted drugs with cytotoxic chemotherapy and radiotherapy in order to overcome the resistance of tumors to single-agent targeted therapies. This review summarizes the current results with cytotoxic and targeted molecular agents in glioblastoma and the development of new chemoradiation strategies under evaluation to increase their effectiveness.

Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.

OBJECTIVES: The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. PATIENTS AND METHODS: Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) > or = 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. RESULTS: The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. CONCLUSIONS: Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients.

OBJECTIVES: The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. PATIENTS AND METHODS: 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > or = 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m(2) per day followed by six cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. RESULTS: The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3-4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. CONCLUSIONS: Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.

A comparative study of general anesthesia, intravenous regional anesthesia, and axillary block for outpatient hand surgery: clinical outcome and cost analysis.

IV regional anesthesia can offer a more favorable patient recovery profile and shorter postoperative nursing care time and hospital discharge time than an isoflurane-based general anesthetic or brachial plexus block technique for hand surgery.