Tumor marker potential of serum matrix metalloproteinases in patients with head and neck cancer.

BACKGROUND: Elevated expression of matrix metalloproteinases (MMPs) is suggested to have tumor marker potential in various tumors. MMPs are capable of disintegrating the basement membrane, which is a main characteristic of tumor invasion. They are specifically inactivated by tissue inhibitors of metalloproteinases (TIMPs). Squamous cell carcinomas of the head and neck (SCCHN) are known to be highly invasive tumors with early locoregional metastatic spread. PATIENTS AND METHODS: To investigate the tumor marker potential of MMPs in SCCHN, MMP-2, -3, -8, -9, -13 and TIMP-1 serum levels were determined in 73 patients and compared to 74 controls. A correlation with T- and N-status, UICC-staging and grading was performed. Additionally, the influence of inflammation on the MMP serum concentration was examined. RESULTS: Significant differences between patients with SCCHN and controls were seen for MMP-3, -8 and -9. A significant correlation was found between MMP-8 concentration and T-status, N-status and UICC-staging. No correlation with the grading of the tumor was observed. Inflammatory diseases did not affect MMP and TIMP levels significantly. CONCLUSION: Some MMPs are elevated in the serum of patients with SCCHN and especially MMP-8 showed interesting tumor marker potential.

Lymphogenic metastatic spread of auricular VX2 carcinoma in New Zealand white rabbits.

INTRODUCTION: The auricular VX2 carcinoma of the New Zealand white rabbit serves as an animal model for human squamous cell carcinomas of the head and neck region (HNSCC), since both tumors tend to metastasize lymphatically, leading to early lymph node and subsequent distant metastasis. The aim of this study was to examine the pattern of lymphogenic metastatic spread in untreated auricular VX2 carcinomas, since the resulting knowledge potentially could help in the development of new treatment strategies for human HNSCC. MATERIALS AND METHODS: VX2 carcinomas were implanted into both ears of 22 New Zealand white rabbits. The animals were sacrificed at days 7, 14, 21, 28 or 32 after tumor implantation, followed by a detailed histopathological examination of their head and neck lymph nodes. RESULTS: On day 7 after tumor implantation 25% of the animals had metastases in the parotid lymph node, which is the first draining lymph node of the tumor region. This number rose to 87.5% by day 28. At this time 12.5% of all animals also had an additional metastasis in the second echelon node. CONCLUSION: A reproducible metastatic spread into the first draining lymph node could be demonstrated for the auricular VX2 carcinoma of the New Zealand white rabbit. The VX2 carcinoma therefore appears to be a highly suitable animal model for studying the sentinel node concept in the context of human HNSCC.

Lymph node topography of the head and neck in New Zealand White rabbits.

Investigations of the lymphogenic metastatic spread of VX2 carcinomas in New Zealand White rabbits require an exact knowledge of the topography of cervical and facial lymph nodes. The topography of neck lymph nodes was evaluated from 16 rabbits macroscopically, histologically and by lymphographic investigations, and the possibility of their surgical removal (neck dissection) was examined. The upper aerodigestive tract and the ear of New Zealand White rabbits drain via four consistent groups of 12-18 lymph nodes. Except for the paratracheal lymph node, they are all easily accessible to surgery. The data presented in this study encourage the use of induced VX2 carcinomas in New Zealand White rabbits as an animal model to study the lymphogenic metastatic spread of squamous cell carcinomas of the head and neck. Such investigations could lead to an improvement of surgical and pharmaceutical treatment of this tumour entity.

Free radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters.

Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group and equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts (Table 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Macrophage colony-stimulating factor as a tumor marker for squamous cell carcinoma of the head and neck.

It has been demonstrated that in patients with epithelial ovarian cancer and malignant germ cell tumors of the ovary, macrophage colony-stimulating factor (M-CSF) is significantly elevated in the serum compared to healthy individuals. Therefore, M-CSF has been suggested as a tumor marker in these malignancies. In the present study, the tumor marker potential of the serum M-CSF concentration in patients with squamous cell carcinomas of the head and neck (SCCHN) was investigated. The serum M-CSF concentration was determined by a quantitative sandwich enzyme immunoassay in 59 patients suffering from SCCHN and 59 healthy controls. A significant difference in the mean serum concentration of M-CSF between the patients with SCCHN and the control group was found (p = 0.002). The M-CSF serum concentration correlated neither with the stage of disease nor with histopathological grading, and no correlation with serum C-reactive protein was found. The serum M-CSF concentration could be of interest as a tumor marker in SCCHN.