Clinical evaluation of tumor markers in breast cancer patients

During the past 4 years, the performances of various tumor markers such as CA15-3, CEA, ferritin, beta 2-microglobulin and TPA have been evaluated in 78 cases of mammary cancer. The results were categorised according to differences in stages, difference in values from patients with recurrent tumors, the incidence of abnormal values and differences in values before and after surgery. When the incidence of values higher than the cutoff value was determined for each of stage I, II and III + IV, the rates for CEA were 14.3%, 4.9% and 27.8%, respectively, whereas those for TPA were 25.0%, 22.2% and 26.7%, respectively. In addition, for CA15-3, the incidences were 0% in stage I, 5.0% in stage II and 57.1% for combined stages III + IV. The average values for patients with recurrent tumors were 3.2 ng/ml CEA, 194.5 ng/ml ferritin, 316.2 U/l TPA and 81.3 U/ml CA15-3. The rates of abnormal values were 40.0% for CEA, 40.0% for ferritin, 85.7% for TPA and 63.6% for CA15-3. Differences in the values after surgical removal of the tumor were observed with these tumor markers: the CEA value was reduced from 1.6 +/- 1.4 to 1.1 +/- 0.5 (p less than 0.01) and the CA15-3 value from 12.2 +/- 8.4 to 9.3 +/- 4.1 (p less than 0.05), respectively, whereas that for ferritin was conversely increased from 48.9 +/- 48.0 to 74.0 +/- 70.0 (p less than 0.01). However, the values for TPA, despite showing a tendency to decrease, did not show any statistically significant alteration. The fluctuations of these marker levels in patients with recurrent tumors reflects the progress of the disease, with a sudden elevation in values indicating imminent death. The diagnostic significance of these markers is not high, but they are considered to be useful in detecting the progress or condition of a recurrent tumor.     

A case of leiomyosarcoma of the prostate

A 50-year-old man with the symptom of anal pain was treated by pelvic exenteration, ileal conduit diversion and artificial anus. The pathologic diagnosis was leiomyosarcoma of the prostate. At 5 months post-operatively, the patient had no evidence of metastasis or recurrence.     

Migration of keratinocytes is impaired on glycated collagen I

Advanced glycation end products are the chemical modification of proteins induced by sugars in a hyperglycemic condition. Extracellular matrix proteins are prominent targets of nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of nonenzymatic glycation of type I collagen on the migration of keratinocytes. The migration of keratinocytes was dramatically promoted on native type I collagen-coated dishes compared with that on uncoated dishes. When type I collagen was glycated with glycolaldehyde, large amounts of advanced glycation end products were produced; the glycated collagen I-coated dishes did not promote the migration of keratinocytes. Glycated collagen I did not affect the proliferative capacity of keratinocytes. However, the adhesion of keratinocytes to glycated collagen I was profoundly diminished in a glycation intensity-dependent manner. alpha2beta1 integrin is responsible for the migration and adhesion of keratinocytes to type I collagen. Pretreatment with glycated collagen I did not affect the expression level or functional activity of alpha2beta1 integrin on keratinocytes. These findings suggest that in the presence of glycated collagen I, keratinocytes lose their adhesive and migratory abilities. As the glycation did not modify the alpha2beta1 integrin on keratinocytes, it is suggested that glycation may diminish the binding capacity of type I collagen.     

Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

Immunohistochemical and biochemical identification of pepsinogen isozymes in the hamster lungs: induction by polychlorinated biphenyls.

Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsinogen positive cells were observed mainly in the epithelia of the terminal bronchioles. They demonstrated morphological features of Clara cells. The pepsinogen isozyme pattern of lung tissue determined by polyacrylamide gel electrophoresis was similar to that of stomach mucosa. Treatment of hamsters with polychlorinated biphenyls at a dose of 500 mg/kg body weight ip caused a 2.8-fold increase in pepsinogen content (p less than 0.01) as well as increase in numbers of pepsinogen positive cells in the lung.     

Repeat operations in the management of clival chordomas: palliative surgery.

Some chordomas have a very poor prognosis because of their aggressive growth nature, but the efficacy of repeat operations for these cases has not been well documented. This report concerns 3 patients with aggressive chordoma of the clivus, who underwent operations 6 to 12 times over a period of 8 to 17 years because of symptomatic regrowth. Overall mean interval between repeat operations was 18 months with a range from 5 to 57 months and survival times were 9 to19 years after the first surgery. Main symptoms before each operation were diplopia and visual disturbance. Repeat palliative operations by intentional extradural debulking of the tumour to decompress offending neural structures, as well as maximal removal of the tumour, using appropriate skull base approaches, can mitigate progressive symptoms, and may result in better quality and some prolongation of life, although our patients gradually deteriorated neurologically throughout the clinical course.     

Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve

We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained-intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve.