Granulocyte-macrophage colony-stimulating factor upregulates matrix metalloproteinase-2 (MMP-2) and membrane type-1 MMP (MT1-MMP) in human head and neck cancer cells

Matrix metalloproteinase-2 (MMP-2) and membrane type 1-MMP (MT1-MMP) play an important role in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC), but the mechanism of their regulation is not clearly understood. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be associated with cancer invasion and metastasis. We hypothesized that GM-CSF may upregulate MMP-2 and/or MT1-MMP expression in HNSCC cells, and may thereby influence their ability to invade and metastasize. We studied the effects of GM-CSF on the production of MMP-2 and MT1-MMP in HNSCC cell lines SAS and HSC-2. Gelatin zymography of conditioned media derived from HNSCC cells revealed a major band of 68 kDa, which was characterized as proMMP-2. GM-CSF stimulated the production of proMMP-2 in both cell lines in a dose-dependent manner. Treatment with 50 ng/ml GM-CSF for 24 h increased the proMMP-2 activity 3.4-fold in SAS cells and 2.3-fold in HSC-2 cells compared with untreated controls. Northern blot analyses demonstrated that GM-CSF led to elevated mRNA levels of MMP-2 and MT1-MMP in both cell lines. The results identify GM-CSF as a regulator of MMP-2 and MT1-MMP expression in certain types of HNSCC, and suggest that GM-CSF may contribute to the invasiveness of HNSCC through the regulation of MMP-2 and MT1-MMP expression.     

The relationship of p53 Protein and lymph node metastases in invasive breast cancer

The p53 expression in invasive breast cancers from 106 patients was correlated with clinicopathological variables to ascertain its usefulness for estimating prognosis. The p53 expression was significantly associated with the number of axillary lymph node metastases and the presence of internal mammary lymph node metastases; however, it was not associated with age, menopausal status, histologic type, or tumor size. Although p53 expression was a significant prognostic factor according to univariate analysis, it did not appear to be an independent prognostic factor according to multivariate analysis. Thus, the prognostic power of p53 expression is likely to be weak and therefore probably of limited clinical value. Nevertheless, the number of patients in our study was small, and we believe that an investigation of a larger series of patients is indicated.     

Blockade of dopamine D1 receptors by SCH 23390 antagonizes discriminative stimulus effects of pentazocine

The purpose of this investigation was to test the hypothesis that the discriminative stimulus properties of pentazocine are mediated through an interaction with dopamine receptors. Rats were trained to discriminate s.c. injections of pentazocine (3.0 mg/kg) from vehicle in a two-choice discrete trial avoidance paradigm. SCH 23390 (0.003–0.056 mg/kg), a selective antagonist of dopamine D₁ receptors, inhibited the discriminative stimulus effects of pentazocine in a dose-dependent fashion, whilst the selective D₂ receptor antagonist sulpiride (20.0–80.0 mg/kg) did not antagonize them. It appears that the dopamine D₁ receptors play an important role in the discriminative stimulus effects of pentazocine.     

Changes in the Quantity and Activity of Cytochrome P-450 Isozymes in Primary Cultured Rat Hepatocytes

Hepatocytes from male Spragne-Dawley rats pretreated with a cytochrome P-450 inducer, 3-methoxy-4-aminoazobenzene (3-MeO-AAB), 3-methylcholanthrene (MC) or phenobarbital (PB), were cultured in vitro , and changes in the quantity and activity of microsomal cytochrome P-450 isozymes in the cells were determined by means of immunochemical methods and a bacterial mutation test, respectively. The results of enzyme-linked immunosorbent assay using monoclonal antibodies against rat P-450 isozymes - test using Salmonella typhimurium TA 98 and carcinogenic aromatic amines. These results indicate that microsomal cytochrome P-450c in primary cultured rat hepatocytes is more stable in culture, in terms of both quantity and activity, than cytochrome P-450d and P-450b/e.     

Dynorphin A(1-13) modulates apomorphine-induced behaviors using multidimensional behavioral analyses in the mouse

The effects of intracerebroventricular injection of dynorphin A(1-13) on apomorphine-induced behavioral changes were investigated in the mouse using multidimensional behavioral analyses based upon a capacitance system. Although lower doses (0.1 or 0.3 mg/kg) of apomorphine were without marked effects on behaviors, a 0.56 mg/kg dose of the drug evoked a significant increase in rearing behaviors. Furthermore 1.0 and 3.0 mg/kg doses of apomorphine produced a marked increment in linear locomotion, circling and rearing. Dynorphin A(1-13) (3.0 or 10.0 microgram) itself had no effects on behaviors. The apomorphine (0.56 and 1.0 mg/kg)-induced increase in rearing behaviors was clearly inhibited by treatment with dynorphin A(1-13) (3.0 and 10.0 microgram). Simultaneously, the marked increases in linear locomotion and circling were displayed by apomorphine (1.0 mg/kg) plus dynorphin A(1-13) (10.0 microgram). The effects of dynorphin A(1-13) (10.0 microgram) on the apomorphine (1.0 mg/kg)-induced increase in rearing were entirely reversed by the opioid antagonist Mr2266. These results suggest that the antagonistic effects of dynorphin A(1-13) on the apomorphine (1.0 mg/kg)-induced increase in rearing are mediated via opioid receptors, possibly K-sites.     

Measurement of an auditory impairment induced by aminoglycosides using a shuttle box method in newborn rats

To investigate the auditory impairment induced by the administration of aminoglycosides in the newborn, the shuttle box method was employed to measure the auditory threshold of rats. Five groups of newborn rats were administered kanamycin sulfate, 250 and 500 mg/kg, streptomycin sulfate, 250 and 500 mg/kg, or 1 ml/kg saline, subcutaneously, from the 10th to the 15th day of birth. The auditory threshold of the control group could be measured by the shuttle box method at the age of 100 days. The auditory threshold of the control group was 52.1 +/- 1.0 dB (N = 14). The auditory thresholds of the animals treated with kanamycin 250 mg/kg and streptomycin 250 mg/kg groups were measured in only 1 (61.0 dB) and 4 (64.8 +/- 4.6 dB), respectively, since the auditory toxicity of these drugs in newborn rats was stronger than adult rats. Auditory threshold of the 250 mg/kg streptomycin group was significantly higher than that of the control group. The animals which could not be measured for the auditory threshold had the ability to acquire conditioned avoidance response when both conditioned stimuli (tone and light) were presented. However, after differentiation of the stimuli, the percent avoidance to tone in these animals was significantly decreased and did not recover by the following trainings, while the percent avoidance to light was similar to that before the differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)