ABSTRACT
OBJECTIVE: Radiotherapy is an option to treat high-grade laryngeal dysplasia. This study aimed to evaluate the use of intensity-modulated radiotherapy, 55 Gy in 20 daily fractions, in treating this disease. METHODS: Acute toxicity was evaluated in all 14 patients treated. In 10 patients, functional voice outcome was measured using the Voice Handicap Index, and the Grade, Roughness, Breath, Asthenia, Strain ('GRBAS') scale. These measurements were performed pre-treatment and three months after intensity-modulated radiotherapy. RESULTS: All but one patient managed to complete radiotherapy. Acute toxicity was significant (one patient developed grade 4 and three patients developed grade 3 dysphagia). Four patients required hospital admission. In 9 out of 10 patients, radiotherapy improved voice quality. CONCLUSION: This radiotherapy regimen using intensity-modulated radiotherapy for laryngeal dysplasia is feasible and provided excellent functional outcome, but acute toxicity was significant. Dose de-escalation can be considered in the framework of clinical trials.
Subject(s)
Laryngeal Diseases/radiotherapy , Precancerous Conditions/radiotherapy , Radiotherapy, Intensity-Modulated , Aged , Aged, 80 and over , Female , Humans , Larynx/pathology , Larynx/radiation effects , Male , Middle Aged , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Treatment Outcome , Voice Disorders/etiologyABSTRACT
BACKGROUND: Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients. METHODS: Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS). RESULTS: Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide. CONCLUSION: Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Lung Neoplasms/blood , Neovascularization, Pathologic/blood , Small Cell Lung Carcinoma/blood , Thalidomide/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Clinical Trials, Phase III as Topic , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Etoposide/administration & dosage , Female , Fibroblast Growth Factor 2/blood , Humans , Intercellular Adhesion Molecule-1/blood , Interleukin-8/blood , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Multicenter Studies as Topic , Multivariate Analysis , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/mortality , Proportional Hazards Models , Randomized Controlled Trials as Topic , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/mortality , Survival Analysis , Treatment Outcome , Vascular Endothelial Growth Factor A/blood , GemcitabineABSTRACT
The expression of the placental isoenzyme of alkaline phosphatase and the alpha subunit of chorionic gonadotropin was examined in a series of cloned lines of Chang liver cells. both placental gene products show large quantitative variation in the amounts made (over 30-fold) among the various clones. This variation occurs independently for both proteins. These results suggest that these placental-specific genes are discordantly regulated. Because karyologic analysis of several clones shows significant variation in the chromosome content, we cannot determine whether such expression results from true independent mechanisms controlling expression or from variation in gene dosage.
Subject(s)
Alkaline Phosphatase/metabolism , Chorionic Gonadotropin/analysis , Placenta/enzymology , Acid Phosphatase/analysis , Cell Line , Chromosomes , Clone Cells , Female , Humans , Liver/analysis , Placenta/ultrastructure , PregnancyABSTRACT
The coincident expression of two structurally distinct isoenzymes of human alkaline phosphatase was demonstrated in two independently derived gestational choriocarcinoma cell lines. These proteins were shown to have enzymatic, antigenic, and physical-chemical properties resembling those of isoenzymes from term placenta and adult liver. The regulation of these isoenzymes has been studied during the exposure of both cell lines to 5-bromodeoxyuridine and dibutyryl cyclic AMP. The responses of the alkaline phosphatase isoenzymes to these agents have also been compared with the response of another protein phenotypic to placenta, the alpha subunit of chorionic gonadotropin. The results show that (i) the separate structural genes coding for placental and liver alkaline phosphatases are regulated in a noncoordinate fashion; (ii) both alkaline phosphatase genes respond independently of the alpha subunit; and (iii) the induction of the placental type isoenzyme occurs via at least two independent pathways.
