Detection of micrometastatic tumor cells in head and neck squamous cell carcinoma. A possible predictor of recurrences?

OBJECTIVE: To evaluate the presence of micrometastatic tumor cells in the peripheral blood samples of the patients with head and neck squamous cell carcinoma (HNSCC) and to determine whether the presence of micrometastatic cells had any biological relevance in terms of local recurrences or metastasis during a follow-up period of 3 years. METHODS: We included 21 consecutive patients with untreated primary HNSCC admitted to the Ear Nose and Throat Department of Akdeniz University Medical School, Antalya, Turkey between February and October 2002. Squamous carcinoma cells in peripheral blood samples of these patients prior to surgery were detected via a magnetic cell separation technique using anti-epithelial cell adhesion molecule antibody, and thereafter evaluated by light microscopy with hematoxylin and eosin staining. RESULTS: Seven out of 21 patients showed squamous carcinoma cells in peripheral blood samples. Patients with stage III and IV tumors were nearly 5 times more likely to show micrometastatic cells compared with those with stage I and II tumors (6/12 versus 1/9). During the follow-up, 2 patients out of 7 with micrometastasis had recurrences. None in the micrometastasis negative group relapsed. CONCLUSION: We suggest that HNSCC patients with detectable tumor cells in peripheral blood represent a subset of patients who should be followed up more closely for possible recurrences.

Effects of MK-801 on nitrite and cGMP levels during focal cerebral ischemia in rats.

Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and initiates the events leading to ischemic brain damage. Glutamate receptor antagonists are being used to reduce neuronal damage observed after hypoxia and ischemia. The glutamate receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclohepten-5,10-imine maleate (MK-801) crosses the blood-brain barrier readily and produces a non-competitive use-dependent blockade of the N-methyl-D-aspartate subtype of glutamate receptor. The aim of this study was to investigate effects of MK-801 administered before and just after the onset of ischemia in rats on nitrite and cyclic guanosine monophosphate (cGMP) levels. Focal cerebral ischemia in rats was produced by permanent occlusion of right middle cerebral artery (MCAO). Nitrite and cGMP levels were measured in both cortex and cerebellum at 0, 10, and 60 min following MCAO. The same parameters were measured in rats treated with MK-801 (0.5 mg/kg, i.p.) 30 min before or just after MCAO. Ipsilateral cortical nitrite levels were increased relative to contralateral cortex after MCAO. No significant changes were observed in cerebellum. The cGMP concentrations in both sides of the cortex and cerebellum were increased at 10 and 60 min compared with 0 min values. cGMP level in the ipsilateral cortex was higher than contralateral cortex, whereas the opposite was found for the cerebellum. MK-801 treatment before or just after MCAO decreased significantly nitrite and cGMP production. Our data indicate that MK-801 treatment before or just after focal ischemia prevents the increase in NO and cGMP production.

Immunohistochemical distribution patterns of collagen type II, chondroitin 4-sulfate, laminin and fibronectin in human nasal septal cartilage.

Collagen type II, chondroitin 4-sulfate, laminin and fibronectin are major components of cartilage matrix. It is important to know their distribution patterns to evaluate relationships between cartilage cells and surrounding cartilage matrix. In the present study, we investigated localization patterns of these macromolecules in human nasal septal cartilage by immunohistochemical methods. Samples of human nasal septal cartilage were obtained from patients with nasal septum deviations who underwent septoplastic operation and were prepared for immunohistochemical examination. Distribution patterns of cartilage matrix macromolecules correlated with those found in other cartilage tissues. Diffuse staining of collagen type II was found in the cartilage matrix, chondroitin 4-sulfate immunostaining was present in the cytoplasm and like a pericellular ring around chondrocytes. Laminin immunostaining was found in the cytoplasm of chondrocytes, and fibronectin was localized in the pericellular matrix and in capsules of human nasal septal cartilage. Moreover, fibronectin was also detected at high levels in the interconnecting segments between adjacent chondrons. In conclusion, similar localisation patterns of the components investigated in human septal cartilage as in other tissues indicate that these macromolecules may play a role in both cell-matrix adhesion and matrix-matrix cohesion in the pericellular microenvironment surrounding nasal septal cartilage chondrocytes as in other cartilage tissues.

The effects of NMDA receptor antagonist MK-801 on lipid peroxidation during focal cerebral ischemia in rats.

The effect of MK-801 on ischemic neuronal damage was studied in a rat model of permanent focal cerebral ischemia in terms of ipsilateral and contralateral cortical and cerebellar tissue lipid peroxides. Forty-five male Swiss Albino rats were assigned into one of four groups: sham operated as controls, subjected to right middle cerebral artery occlusion (MCAO) or injection of MK-801 (0.5 mg/kg i.p.) either 30 min before or just after right MCAO. Changes in lipid peroxides were expressed as nmol malondialdehyde (MDA) and conjugated diene (CD)/mg protein. MDA values after 60 min of ischemia relative to contralateral cortex and CD levels in 0, 10 and 60 min after ischemia were found to be higher in ipsilateral cortex than those in contralateral cortex. On the other hand, contralateral cerebellar MDA levels in 0 and 60 min of ischemia and CD levels in 0, 10 and 60 min after ischemia were found to be higher than those in ipsilateral cerebellum. Pharmacological inhibition of glutamate receptor by MK-801 before or just after permanent MCAO decreased significantly the MDA and CD levels in both cortex and cerebellum. Although no significant differences found in MDA values between rats pre- and posttreated with MK-801, CD levels in posttreated group seemed significantly lower than those in pretreated group. On the whole, these results suggest that MDA and CD represent early biochemical marker of lipid peroxidation in ischemic tissues, reflecting the radical-mediated tissue damage.

Lipid peroxidation in rat brain during focal cerebral ischemia: prevention of malondialdehyde and lipid conjugated diene production by a novel antiepileptic, lamotrigine.

The effects of Lamotrigine (LTG) which blocks ischemia induced glutamate (Glu) release, on lipid peroxidation have been evaluated in cortical and cerebellar tissues of rat brain during focal cerebral ischemia. A total of 45 rats were randomly assigned into one of four groups; sham operated animals as controls, animals subjected to middle cerebral artery occlusion (MCAO) and treatment groups with LTG (20 mg/kg i.p.) either 30 min before or just after MCAO. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde (MDA) and conjugated diene (CD) per milligram of protein. MDA values following 60 min of ischemia relative to contralateral cortex and CD levels in 0, 10 and 60 min of ischemia were found to be higher in the ipsilateral cortex than those in the contralateral cortex. On the other hand, contralateral cerebellar MDA levels after 0 and 60 min of ischemia and CD levels after 0, 10 and 60 min of ischemia were higher than those in the ipsilateral cerebellum. Pharmacological inhibition of Glu release significantly decreased the MDA and CD production in both cortex and cerebellum. Pre- or post-ischemic administration of LTG did not significantly change CD levels, but MDA levels in contralateral cortex were found to be significantly decreased than those in ischemic cortex in both pre- and post-treated group.