Frequent expression of MAGE1 tumor antigens in bronchial epithelium of smokers without lung cancer.

Melanoma antigens (MAGE) are frequently expressed in lung cancer and are promising targets of anticancer immunotherapy. Our preliminary data suggested that MAGE may be expressed during early lung carcinogenesis, raising the possibility of targeting MAGE as a lung cancer prevention strategy. The purpose of this study was to investigate MAGE activation patterns in the airways of chronic smokers without lung cancer. MAGE-A1, -A3 and -B2 gene expression was determined in bronchial brush cells from chronic former smokers without lung cancer by reverse transcription-PCR (RT-PCR). The results were correlated with clinical parameters. The 123 subjects had a median age of 57 years, a median of 40 pack-years smoking history, and had quit smoking for at least one year prior to enrollment. Among the subjects, 31 (25%), 38 (31%), and 46 (37%) had detectable MAGE-A1, -A3 and -B2 expression, respectively, in their bronchial brush samples. Expression of MAGE-A1 and -B2 positively correlated with pack-years smoking history (P=0.03 and 0.03, respectively). The frequency of expression did not decrease despite a prolonged smoking cessation period. In conclusion, MAGE-A1, -A3 and -B2 genes are frequently expressed in the bronchial epithelial cells of chronic smokers without lung cancer, suggesting that chronic exposure to cigarette smoke activates these genes even before the malignant transformation of bronchial cells in susceptible individuals. Once activated, the expression persists despite long-term smoking cessation. These data support the targeting of MAGE as a novel lung cancer prevention strategy.

Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs.

The lungs and oral cavity of smokers are exposed to tobacco carcinogens. We hypothesized that tobacco-induced molecular alterations in the oral epithelium are similar to those in the lungs, and thus the oral epithelium may be used as a surrogate tissue for assessing alterations in the lungs. We used methylation-specific PCR to analyze promoter methylation of the p16 and FHIT genes at baseline and 3 months after intervention in 1,774 oral and bronchial brush specimens from 127 smokers enrolled in a randomized placebo-controlled chemoprevention trial. The association between methylation patterns in oral tissues and bronchial methylation indices (methylated sites / total sites per subject) was analyzed in a blinded fashion. At baseline, promoter methylation in bronchial tissue was present in 23% of samples for p16, 17% for FHIT, and 35% for p16 and FHIT; these percentages were comparable to methylation in oral tissue: 19% (p16), 15% (FHIT), and 31% (p16 and FHIT). Data from both oral and bronchial tissues were available for 125 individuals, in whom the two sites correlated strongly with respect to alterations (P < 0.0001 for both p16 and FHIT). At baseline, the mean bronchial methylation index was far higher in patients with oral tissue methylation (in either of the two genes; 39 patients) than in patients without oral tissue methylation (86 patients): 0.53 +/- 0.29 versus 0.27 + 0.26 methylation index (P < 0.0001). Similar correlations occurred at 3 months after intervention. Our results support the potential of oral epithelium as a surrogate tissue for assessing tobacco-induced molecular damage in the lungs and thus have important implications for designing future lung cancer prevention trials and for research into the risk and early detection of lung cancer.

Multifocal osteosarcoma involving unusual sites.

We report a rare case of multifocal osteosarcoma (MFOS) with involvement of skeleton, lung, bone marrow, and soft tissues, presenting with paraparesis, cranial nerve palsies, subcutaneous nodules, anemia, and thrombocytopenia. MFOS with involvement of unusual sites presents problems in diagnosis and has a poor prognosis. The literature on 11 cases of MFOS with extraosseus, extrapulmonary involvement reported previously has been reviewed.

Small cell lung cancer: an update on therapeutic aspects.

Small cell lung cancer comprises approximately 20% of all lung cancers and continues to be a difficult management issue. More than two-thirds of cases present with extensive disease, which has spread beyond the himithorax and regional ipsilateral nodes. While response rates to chemotherapy are relatively high, durable responses are rare, and long-term survival rates are anecdotal. Although many attempts have been made to develop new therapies, a combination of etoposide with either cisplatin or carboplatin remains the most widely used first-line therapy for extensive disease. For those with limited disease, chemotherapy with concomitant radiotherapy (given with the first or second cycles of chemotherapy) is considered the standard of care. Over the last decade, several new drugs and targeted agents have been identified with the aim to improve outcome of this malignancy. In this review we highlight recent developments in the management of this tumour.

Randomized study comparing 4'-epi-doxorubicin (epirubicin) versus doxorubicin as a part of induction treatment in adult acute lymphoblastic leukemia.

Doxorubicin or daunorubicin are routinely used to induce remission in acute lymphoblastic leukemia (ALL). Efficacy of epirubicin (an analog of doxorubicin), however, has not been adequately evaluated in ALL management. This randomized study was undertaken to compare the relative efficacy of epirubicin vs. doxorubicin as part of induction chemotherapy in adult ALL. Between January 1990 and June 1998, 79 previously untreated adult ALL patients (age 11-55 years, median 20 years) were randomized to receive either doxorubicin (Group A, n = 39) or epirubicin (Group B, n = 40) as a part of induction therapy. Vincristine and prednisolone were common in each group. The induction treatment was followed by identical consolidation and maintenance therapy. The two groups were compared as regards pretherapy clinical and laboratory parameters, dose intensity of therapy, therapeutic efficacy, myelotoxicity, and survival. Epirubicin was as effective as doxorubicin in terms of complete remission rate (80% vs. 78.3%; P = 0.87) and relapse rate (57.1% vs. 51.7%; P = 0.68). Five-year overall survival (30% vs. 30%, P = 0.98) and disease-free survival (40% vs. 39%, P = 0.92) at median follow-up of 68 months was also similar in the two groups. The incidence of Grade 4 myelotoxicity was comparable in the two groups. Patients 20 years of age or less had better CR rates (90% vs. 65%; P = 0.011) and median overall survival (39 vs. 11 months; P = 0.008) compared to those who were older. From this study epirubicin appears as effective as doxorubicin as part of induction therapy for adult ALL. However, the results need to be validated on the basis of immunophenotype and cytogenetic prognostic characterization.