A new simply and effective fractionation method for cylindrospermopsin analyses.

A new simply and effective fractionation method for cylindrospermopsin (CYN) analyses was developed. The extract from cells of Cylindrospermopsis raciborskii was resuspended with 0.1 M carbonate buffer at pH 10.5, and pass through the double-cartridges column which was consisted of a styrene polymer cartridge and an anion exchange cartridge. CYN and deoxy-CYN were adsorbed with the anion exchange cartridge. After separation of the anion exchange cartridge, adsorbed compounds were eluted from the cartridge with 50% methanol containing 1% formic acid solution. CYN and deoxy-CYN were selectively condensed in the eluted solution. When CYN was analyzed by LC-photodiode array or LC/MS, only two peaks of CYN and deoxy-CYN were detected quantitatively. The results suggest that the fractionation method is a useful method for CYN analyses and must be utilized for CYN purification.     

Hypofractionnement en radiothérapie : l’éternel retour

Hypofractionation is not a new idea in radiotherapy. The use of a few high-dose fractions has been proposed by some pioneers of our specialty in the early years of the 20th century. Hypofractionation then reappeared several times in the next decades, based on successive radiobiological concepts, a number of them having been shown to be wrong. The nominal single dose (NSD), for example, so fashionable in the 1970's, dramatically underestimated the late toxicity of the high-dose fractions. Consequently, the NSD was directly responsible for a significant increase of the incidence and of the severity of late complications in large cohorts of patients. The linear-quadratic model (LQ) unequivocally improved our understanding of fractionation sensitivity, but one has to keep in mind its limitations, both in the areas of low and high doses per fraction. For more than a decade, prostate cancer has been the subject of fierce discussions about its sensitivity to fractionation. A number of studies have suggested an unusually low (for a malignant tumor) alpha/beta ratio. However, the available data do not allow a precise evaluation of this ratio; “very low” (1.5 Gy), with an advantage of hypofractionation in terms of local control? Or simply “low” (3–4 Gy), only allowing a reduction of the total number of fractions (with a dose adequately reduced)? While waiting for complementary data, it is advised to remain very careful when modifying the classical schemes towards hypofractionation.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.     

Transmission blocks: clinical and biological rationales

This paper describes the clinical and biological rationales for the use of transmission blocks. Clinical advantages over the use of full-thickness blocks applied part way through the course of therapy include the use of only one set of fields, blocks, and beam calculations, and less complex chart recording. There is a net saving in time required for the preparation and treatment of the patient. There is also a quality assurance advantage since the impact of a potential error in block positioning is reduced. In terms of biological advantages, it is demonstrated that the linear-quadratic iso-effect model can be applied to predict an improvement of up to 10% in the therapeutic ratio if transmission blocks are used instead of full-thickness blocks.     

Chemoradiotherapy for lung cancer: current status and perspectives

For many years, thoracic radiotherapy had been regarded as the standard treatment for patients with unresectable locally advanced non-small cell lung cancer. However, meta-analyses show that cisplatin-containing chemoradiotherapy is significantly superior to radiothe-rapy alone in terms of survival. Moreover, concurrent chemoradiotherapy yields a significantly increased response rate and enhanced survival duration when compared with the sequential approach. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is considered to be four cycles of combination chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation (45Gy). If patients achieve complete remission, prophylactic cranial irradiation should be administered. A 5-year survival rate of approximately 25% is expected with the state-of-the-art treatment for limited-stage small cell lung cancer. Chemoradiotherapy is considered to be a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Several new strategies are currently being investigated to improve the survival of these patients. The incorporation of target-based drugs such as gefitinib is considered to be the most promising strategy for unresectable locally advanced non-small cell lung cancer. The incorporation of irinotecan is also a promising strategy to improve the survival of patients with limited-stage small cell lung cancer. The Japan Clinical Oncology Group is conducting clinical trials to develop new treatment strategies for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer.     

Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas

Purpose: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with recurrent high-grade gliomas by comparing two different treatment regimens, single dose or fractionated radiotherapy.

Methods and Materials: Between April 1991 and January 1998, 71 patients with recurrent high-grade gliomas were treated with SRT. Forty-six patients (65%) were treated with single dose radiosurgery (SRS) and 25 patients (35%) with fractionated stereotactic radiotherapy (FSRT). For the SRS group, the median radiosurgical dose of 17 Gy was delivered to the median of 50% isodose surface (IDS) encompassing the target. For the FSRT group, the median dose of 37.5 Gy in 15 fractions was delivered to the median of 85% IDS.

Results: Actuarial median survival time was 11 months for the SRS group and 12 months for the FSRT group (p = 0.3, log-rank test). Variables predicting longer survival were younger age (p = 0.006), lower grade (p = 0.0006), higher Karnofsky Performance Scale (KPS) (p = 0.0005), and smaller tumor volume (p = 0.02). Patients in the SRS group had more favorable prognostic factors, with median age of 48 years, KPS of 70, and tumor volume of 10 ml versus median age of 53 years, KPS of 60, and tumor volume of 25 ml in the FSRT group. Late complications developed in 14 patients in the SRS group and 2 patients in the FSRT group (p < 0.05).

Conclusion: Given that FSRT patients had comparable survival to SRS patients, despite having poorer pretreatment prognostic factors and a lower risk of late complications, FSRT may be a better option for patients with larger tumors or tumors in eloquent structures. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.     

Effects of radiation fractionation on four squamous cell carcinoma lines with dissimilar inherent radiation sensitivity

Summary The effect of radiation fractionation was investigated using a new 96-well-plate clonogenic assay in four squamous cell carcinoma lines. Earlier experiments had shown that two of the cell lines (UT-SCC-1A and UM-SCC-14A) were inherently relatively sensitive to irradiation, and two (UM-SCC-1 and UM-SCV-1A) relatively resistant. All of the four carcinomas from which the cell lines were established had poor clinical outcome. The radiation doses were given as a single exposure, or split into two or three equal fractions with a 24-h interval. The two inherently sensitive cell lines showed enhanced survival after radiation fractionation as compared with a single dose, whereas the resistant cell lines did not. The result suggests that both the inherent resistance of cancer cells to irradiation and the repair of sublethal radiation damage may lead to treatment failure, and that shortening of the total irradiation time may overcome cancer cell recovery between fractions in some, but not in all carcinomas.Abbreviation SCC squamous cell carcinoma The study was financially supported by the Finnish Cancer Society     

Microarray analysis of gene expression in rat alveolar epithelial cells exposed to fractionated organic extracts of diesel exhaust particles

Diesel exhaust particles (DEP) affect health adversely. Our previous studies revealed that DEP extracts up-regulated expression of genes related to drug metabolism, antioxidant enzymes, cell cycle/apoptosis and coagulation, and in addition, n-hexane soluble fraction (n-HSF) of DEP extracts contains aliphatic and polycyclic aromatic hydrocarbons, and n-hexane insoluble fraction (n-HISF) contains oxygenated compounds and has strong oxidative property. However, the relationship between the properties of chemicals in DEP extracts and the gene expression has not been fully elucidated. Here, we used a microarray analysis to identify and characterize genes whose expression is regulated by exposure to fractions of DEP extracts. A dichloromethane-soluble fraction (DMSF) of DEP was further fractionated into n-HSF and n-HISF. We exposed rat alveolar epithelial (SV40T2) cells to these fractions (30 μg/ml) for 6 h and identified regulated genes. DMSF predominantly up-regulated genes associated with drug metabolism (Cyp1a1, Gsta3), oxidative stress response (HO-1, Srxn1) and cell cycle/apoptosis (Okl38). Genes up-regulated by n-HSF were mainly associated with drug metabolism (Cyp1a1, Gsta3). The genes up-regulated by n-HISF included antioxidant enzymes (HO-1, Srxn1); genes response to cell damage, such as those functioning in cell cycle regulation or apoptosis (Okl38); and genes in coagulation pathways. Our present results suggested that n-HSF and n-HISF regulated characteristic genes which respond to chemical properties of each fraction.