Usefulness of chromosome alteration analysis in cell lines derived from laryngeal tumors for evaluation of laryngeal neoplasms

A classical cytogenetic analysis was applied to analyse karyotypes of 9 cell lines derived from laryngeal cancer. The most frequent aberration was a deletion of the whole sex chromosome Y. An abundance of somatic chromosome alterations was further analysed to find correlation with tumour staging and grading. A conventional cytogenetic analysis seems to be not sufficient to recognize chromosome alterations specific for a given tumor stage. On the other hand, an analysis in respect to histologic grading has indicated for an association between rearrangement of 9 chromosome and a high tumor aggressiveness. It seems that a combination of conventional cytogenetics with molecular methods (FISH, CGH) would be helpful in diagnosing of laryngeal cancer.     

Endoscopic laser surgery for laryngeal cancer

Endoscopic laser surgery is a novel treatment modality for laryngeal cancer. CO₂ laser combined with an operating microscope is the most frequently used instrumentation. In Finland we started large-scale laser surgery in 1994 in all five university hospitals, covering a population of about five million people. By 1998 we had operated on 140 patients, of whom 11 were females. Eighty-three per cent of the lesions were glottic. Because of the low number of stage III–IV patients, the recurrence and survival analyses included 132 patients with in situ, stage I or stage II tumours, numbering 8, 96 and 28 respectively. The mean follow-up time was 38 months. The 2-year recurrence frequencies were 5% for stage I, 31% for stage II, and 11% altogether. No patients developed recurrences after 2 years. Seven patients underwent a salvage laryngectomy and the adjusted cumulative survival rate was 95%. After laser surgery the quality of voice was good or excellent in 70% and only three patients suffered from severe aphonia. This study showed that the results of endoscopic laser surgery are comparable with those of radiation therapy, but this type of treatment is more convenient for the patients and much cheaper for society. Received: 20 June 2000 / Accepted: 10 April 2001     

Diagnostic aspects of primary tubal malignancy

Eleven cases of primary tubal malignancy are reported to characterize clinical symptoms and diagnostic procedures. The importance of a yellow vaginal discharge is emphasized as being a diagnostic sign.     

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     

p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells

Recent studies indicate that the specificity of p38 mitogen-activated protein kinase (MAPK)-mediated cellular stress responses is determined by the expression pattern of the distinct p38 isoforms. Here, we have analysed the function of distinct p38 isoforms in the growth and invasion of head and neck squamous cell carcinomas (HNSCCs). Activation of p38 MAPK by arsenite resulted in inactivation of the ERK1,2 signaling pathway by dephosphorylation of MEK1,2 in primary human epidermal keratinocytes (HEKs), whereas in HNSCC cells this p38-mediated inhibition of the ERK1,2 pathway was absent. Quantitation of p38 pathway component mRNA expression in HNSCC cell lines (n=42) compared to HEKs (n=8) revealed that p38alpha and p38delta isoforms are predominantly expressed in both cell types and that MKK3 is the primary upstream activator expressed. Inhibition of endogenous p38alpha or p38delta activity by adenoviral delivery of corresponding dominant-negative p38 isoforms potently reduced MMP-13 and MMP-1 expressions, and suppressed the invasion of HNSCC cells through collagen. Dominant-negative p38alpha and p38delta inhibited squamous cell carcinoma (SCC) cell proliferation and inhibition of p38alpha activity also compromised survival of SCC cells. p38alpha and p38delta were predominantly expressed in HNSCCs (n=24) and nonneoplastic epithelium in vivo (n=6), with MKK3 being the primary upstream activator. Activation and expression of p38alpha and p38delta by tumor cells was detected in HNSCCs in vivo (n=16). Adenoviral expression of dominant-negative p38alpha or p38delta in cutaneous SCC cells potently inhibited their implantation in skin of severe combined immunodeficiency mice and growth of xenografts in vivo. Our results indicate that p38alpha and p38delta specifically promote the malignant phenotype of SCC cells by regulating cell survival, proliferation and invasion, suggesting these p38 MAPK isoforms as potential therapeutic targets in HNSCCs.