Makoto Fukuda

Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer.

PurposeVascular endothelial growth factor (VEGF) is an important factor involved in angiogenesis. Many studies have reported that the expression of VEGF in breast cancer is an unfavorable prognostic factor. However, there are few studies that have analyzed blood VEGF levels because most used serum VEGF, generally thought to originate from platelets. We measured plasma VEGF levels, which evaluate the level of tumor-derived VEGF, in various breast diseases.MethodWe analyzed 15 patients with benign breast disease, 187 patients with primary breast cancer, 32 patients with no postoperative recurrence, and 56 patients with recurrence. Plasma VEGF levels were measured by ELISA.ResultsPlasma VEGF levels were higher in malignant than in benign breast disease, and were also high in patients with recurrence or distant metastasis. In primary cases, higher VEGF levels were clearly correlated with menopause and overexpression of p53, and postmenopausal patients with high levels had a significantly lower disease-free survival rate.ConclusionThese results suggest that plasma VEGF levels in breast cancer have a clinical significance in that they are associated with the extent or metastasis of malignant lesions and are involved in angiogenesis in postmenopausal patients.

An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

Effects of fluid flow on elution of hydrophilic modifier from dialysis membrane surfaces

When uremic blood flows through dialyzers during hemodialysis, dialysis membrane surfaces are exposed to shear stress and internal filtration, which may affect the surface characteristics of the dialysis membranes. In the present study, we evaluated changes in the characteristics of membrane surfaces caused by shear stress and internal filtration using blood substitutes: water purified by reverse osmosis and 6.7 wt% dextran70 solution. We focused on the levels of a hydrophilic modifier, polyvinylpyrrolidone (PVP), on the membrane surface measured by attenuated total reflectance Fourier transform infrared spectroscopy. Experiments involving 4 h dialysis, 0–144 h shear-stress loading, and 4 h dead-end filtration were performed using polyester-polymer alloy (PEPA) and polysulfone (PS) membranes. After the dialysis experiments with accompanying internal filtration, average PVP retention on the PEPA membrane surface was 93.7% in all areas, whereas that on the PS membrane surface was 98.9% in all areas. After the shear-stress loading experiments, PVP retention on the PEPA membrane surface decreased as shear-stress loading time and the magnitude of shear stress increased. However, with the PS membrane, PVP retention scarcely changed. After the dead-end filtration experiments, PVP retention decreased in all areas for both PEPA and PS membranes, but PVP retention on the PEPA membrane surface was lower than that on the PS membrane surface. PVP on the PEPA membrane surface was eluted by both shear stress and internal filtration, while that on the PS membrane surface was eluted only by internal filtration.

Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis.

Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer.

Computational Evaluation of Dialysis Fluid Flow in Dialyzers With Variously Designed Jackets

Dialyzer performance strongly depends on the flow of blood and dialysis fluid as well as membrane performance. It is necessary, particularly to optimize dialysis fluid flow, to develop a highly efficient dialyzer. The objective of the present study is to evaluate by computational analysis the effects of dialyzer jacket baffle structure, taper angle, and taper length on dialysis fluid flow. We modeled 10 dialyzers of varying baffle angles (0, 30, 120, 240, and 360 degrees ) with and without tapers. We also modeled 30 dialyzers of varying taper lengths (0, 12.5, 25.0, and 50.0 mm) and angles (0, 2, 4, and 6 degrees ) based on technical data of APS-SA dialyzers having varying surface areas of 0.8, 1.5, and 2.5 m(2) (Rexeed). Dialysis fluid flow velocity was calculated by the finite element method. The taper part was divided into 10 sections of varying fluid resistances. A pressure of 0 Pa was set at the dialysis fluid outlet, and a dialysis fluid flow rate of 500 mL/min at the dialysis fluid inlet. Water was used as the dialysis fluid in the computational analysis. Results for dialysis fluid flow velocity of the modeled dialyzers indicate that taper design and a fully surrounded baffle are important in making the dialysis fluid flow into a hollow-fiber bundle easily and uniformly. However, dialysis fluid flow channeling occurred particularly at the outflowing part with dialyzers having larger taper lengths and angles. Optimum design of dialysis jacket structure is essential to optimizing dialysis fluid flow and to increasing dialyzer performance.

Diagnostic problems of evaluating vertebral metastasis from breast carcinoma with a higher degree of malignancy

Bone metastases from breast carcinoma are frequently observed as postoperative pathologic conditions; however, in many cases, diagnosis and treatment are difficult. Although most diagnoses of bone metastases are made by plain radiography (X‐P) or bone scintigraphy, the use of magnetic resonance imaging (MRI) has enabled detailed imaging of foci, and many more lesions have become detectable. In the current study, the authors evaluated the relation between the diagnosis of bone metastases of breast carcinoma and clinicopathologic factors, especially those of proliferative activity and effects of treatment.

Development of a device for chemiluminescence determination of superoxide generated inside a dialysis hollow-fiber membrane

Reactive oxygen species (ROS) generated during hemodialysis treatment cause dialysis complications because of the high reactivity of ROS. To prevent dialysis complications caused by oxidative stress, it is important to evaluate the generation and dismutation of ROS during hemodialysis treatment. In this study, our aim was to develop a device to determine superoxide (O2−) generated inside a dialysis hollow fiber, and also to examine whether this device could detect O2− separated from plasma using hollow fibers. Experimental apparatus was set up so that hypoxanthine (HX) solution flowed inside the hollow fibers and 2-methyl-6-p-methoxyphenylethynyl-imidazopyrazinone (MPEC) solution flowed outside the hollow fibers. Then, xanthine oxidase (XOD) solution was added to the HX solution to generate O2−, and chemiluminescence resulting from the reaction of O2− with MPEC was measured with an optical fiber. Chemiluminescence intensity was measured at different HX concentrations, and the peak area of relative luminescence intensity yielded a first-order correlation with the HX concentration. Based on the relationship between HX and O2− concentrations determined by the cytochrome c reduction method, the relative luminescence intensity measured by this device was linearly dependent on the O2− concentration inside the hollow fibers. After modifications were made to the device, XOD solution injection into plasma including HX resulted in an increase in the relative luminescence intensity. We concluded that this novel device based on chemiluminescence is capable of determining aqueous O2− generated inside a hollow fiber and also of detecting O2− in plasma.