Cyclin-dependent kinase (CDK) inhibitor olomoucine enhances gamma-irradiation-induced apoptosis and cell cycle arrest in Raji cells.

Gamma-irradiation leads to apoptosis and cell cycle arrest in eukaryotic cells. Olomoucine is a novel purine analog acting as a cyclin-dependent kinase inhibitor. The effects of olomoucine in gamma-irradiation mediated cell growth inhibition and apoptosis were studied in the Raji cell line (Burkitt's lymphoma). Gamma-irradiation caused a G2 arrest, increasing the G2/M fragment of the cells. Apoptosis by gamma-irradiation was apparent both by DNA-electrophoresis and PARP-1 cleavage. The combination of olomoucine with irradiation caused an increased G2 arrest and decreased cell survival and DNA synthesis in the non-apoptotic fraction of the remaining cells. Irradiation, as well as olomoucine and the combination of both, induced apoptosis. It seems that olomoucine delays the apoptotic process and inhibits DNA fragmentation, but it decreased survival, cell cycle progression and proliferation of irradiated cells.

Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (non-nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial.

PURPOSE: Tumor volume (TV) is one of the main reported factors determining the outcome of treatment in head-and-neck carcinomas. In this study, the prognostic impact of TV was explored in the context of a randomized trial with the patients assigned to receive standard radiotherapy (RT) alone or RT plus platinum compounds (RT alone, RT plus cisplatin, or RT plus carboplatin). METHODS AND MATERIALS: The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied. Taking into account the magnification factor of the scan and CT slice thickness, a computer with specifically designed software calculated the TV in cubic centimeters. RESULTS: The median overall survival for the whole group of patients was 21.6 months (95% confidence interval, 13.0-30.2) and the 3-year survival rate was 40%. The addition of platinum compounds to RT (Groups 2 and 3) significantly improved the survival rate (RT alone vs. RT plus cisplatin, hazard ratio 0.36, p = 0.002; RT alone vs. RT plus carboplatin, hazard ratio 0.53, p = 0.029). In univariate analysis, the most significant parameters for survival were treatment group, total gross tumor volume (TGTV), complete response, nodal GTV, primary GTV, and performance status. In multivariate analysis, treatment group, TGTV, gender, and primary site were independent prognostic factors for survival. A prognostic threshold of 22.8 cm(3) was detected for TGTV. Patients with a TGTV of <22.8 cm(3) were more likely to achieve a complete response and had a median survival of 45.3 months, and those with a TGTV >22.8 cm(3) had a median survival of 12.3 months (log-rank test, p = 0.0102). CONCLUSION: The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3) derived. Our data indicated that locally advanced head-and-neck carcinomas should not be treated by standard (once-daily) RT alone. Tumor size and disease subsite should be taken into account in future randomized trials to increase their statistical power.

Imaging of primary bone tumors of the spine.

Primary tumors of the spine are relatively infrequent lesions compared with metastatic disease, multiple myeloma, and lymphoma. A wide variety of benign and malignant neoplasms can involve the spine. The imaging features of these lesions are often characteristic. We present an overview of the imaging modalities in primary tumors of the spine in order to provide a useful tool in current radiologic practice. The role of CT and MRI is discussed.

Octreotide for palliative treatment of hepatic metastases from non-neuroendocrine primary tumours: evaluation of quality of life using the EORTC QLQ-C30 questionnaire.

BACKGROUND AND AIM: While octreotide has been used in palliative treatment of hepatocellular carcinoma and neuroendocrine tumours with good results, little is known about the possible role of this in palliative treatment of hepatic metastases. MATERIAL AND METHODS: We present our experience from the use of octreotide in palliative treatment of symptomatic liver metastases in 16 patients (11 males, five females, age ranged 43-69 years) with proven hepatic metastases from different primary tumours (six with non-small lung cancer, four with colon carcinoma, two with primary pancreatic head carcinoma, two with prostate cancer and two with adenocarcinoma of the stomach). All patients were administered 20 mg long-acting octreotide IM (octreotide LAR) once the first day, octreotide SC 0.5 mg three times daily on days 2-14 and then 20 mg long-acting octreotide IM every month. Quality of life was assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30). Tumour response was evaluated by using ultrasonography. RESULTS: One month after baseline, octreotide resulted in significant (P < 0.01, Wilcoxon test) improvement and stabilization of all major related EORTC QLQ-C30 parameters such as global quality of life, pain, fatigue, insomnia, appetite loss as well as physical, emotional, cognitive, social and role functioning. Except for mild hyperglycaemia in six out of 16 patients and mild gastrointestinal complications in one patient, no other severe side effect due to octreotide was reported. Two patients died two months after the initiation of the study due to generalized metastatic disease, while the remaining 14 patients were still alive seven months after the initiation of the study. The hepatic metastases were stabilized and no new lesions were detected by ultrasonography. CONCLUSIONS: Although further studies are warranted, we consider the use of octreotide a good alternative in palliative treatment of symptomatic liver metastases in patients with end-stage malignant disease.