Biomedical subjects

Makoto Takayama

Publications and source records attributed to Makoto Takayama.

8 recordsLinked to original sources

PubMed2006

Multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects of a population of more than 5,000.

PURPOSE: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study. PATIENTS AND METHODS: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanese hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7-2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25-60 Gy). RESULTS: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% (p = 0.018). Three-year overall survival rates of the total dose > or =51 Gy and that of < or =50 Gy were 58.0% and 42.8%, respectively (p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity. CONCLUSIONS: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.

Adult↗

PubMed2006

Comparison of the antiatherosclerotic effects of dihydropyridine calcium channel blocker and HMG-CoA reductase inhibitor on hypercholesterolemic rabbits.

The antiatherosclerotic effects of the dihydropyridine-type calcium channel blocker, benidipine hydrochloride (benidipine), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin sodium (pravastatin), were compared in hypercholesterolemic rabbits. Male, New Zealand white rabbits were fed a 0.5% cholesterol diet. Pravastatin (10 mg/kg) or benidipine (10 mg/kg) was orally administered once daily after start of feeding. After 8 weeks of cholesterol feeding, serum cholesterol was increased and endothelial function of thoracic aorta was impaired. Pravastatin prevented elevation of serum cholesterol and aortic tunica intima hyperplasia. Although benidipine had little effect on serum cholesterol, it significantly inhibited aortic tunica intima hyperplasia and impairment of endothelial function. Expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mRNA in aorta of hypercholesterolemic rabbit were higher than those of normal rabbit. Benidipine significantly prevented upregulation of VCAM-1 mRNA expression and showed a tendency to inhibit elevation of LOX-1 mRNA expression. Pravastatin significantly prevented upregulation of both VCAM-1 and LOX-1 mRNA expression. The results demonstrate that pravastatin inhibits increase of serum cholesterol and vascular dysfunction in hypercholesterolemic rabbit. Benidipine is effective in preventing vascular hyperplasia without altering serum cholesterol levels and this may be due to inhibition of expression of VCAM-1.

Animals↗

PubMed2006

Effects of combination of angiotensin receptor blocker and calcium channel blocker on ox-LDL levels and cardiovascular dysfunction in Dahl rats.

In an effort to assess the cardiovascular benefits of combined angiotensin receptor blockage and calcium channel antagonism, we assessed the chronic effects of the angiotensin type 1 receptor blocker candesartan, the calcium channel blocker benidipine, and the use of a combination therapy in Dahl salt-sensitive (DS) rats. DS rats receiving a high salt diet were treated with either benidipine (4 mg/kg), candesartan (1 mg/kg) or both. Rat blood pressure was measured using a tail-cuff method. Following 12 weeks, the effect on heart weight, plasma-oxidized low-density lipoprotein (ox-LDL) level, endothelium-dependent vasorelaxation, and histology of the heart and aorta was assessed. Blood pressure, heart weight and plasma ox-LDL levels increased, while endothelium-dependent vasorelaxation decreased in the DS rats. Candesartan and benidipine inhibited the increase in blood pressure and heart weight, and the decrease in endothelium-dependent vasorelaxation. The use of benidipine alone or a combination significantly inhibited the increase in ox-LDL levels, whereas candesartan alone had no significant effect on ox-LDL levels. The present findings indicate that, if the monotherapy using ARB could not achieve adequate control of blood pressure, the combination therapy with ARB and benidipine provides the additional reductions in hypertension and cardiac hypertrophy. Moreover, the combination therapy inhibits cardiovascular dysfunction and ox-LDL levels more effectively than use of ARB alone. These results contribute to the possibility of lowering ox-LDL levels as a means of enhancing cardiovascular protection.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Frequency and characteristics of isolated para-aortic lymph node recurrence in patients with uterine cervical carcinoma in Japan: a multi-institutional study.

OBJECTIVE: In most cases of uterine cervical carcinoma recurrence, the first site of distant metastasis or recurrence is reported to be the para-aortic region. Some reports have demonstrated that, in cases of isolated para-aortic lymph node recurrence treated by radiation therapy, patients survived for a long period, which suggests that isolated para-aortic lymph node recurrence in uterine cervical carcinoma is a regional disease rather than systemic disease. Determining the predictive characteristics of isolated para-aortic lymph node recurrence in patients at the time of the initial treatment for primary uterine cervical carcinoma is important, so we conducted the current multi-institutional study. PATIENTS AND METHODS: Patients (n=3137) with uterine cervical carcinoma of stages Ia to IVa were treated in twelve Japanese hospitals between 1994 and 2003. The current study investigated the frequency and characteristics of patients with isolated para-aortic lymph node recurrence as well as the characteristics of clinical stage, histopathology, serum squamous cell carcinoma antigen level, the treatment method at the initial treatment, the duration between the initial treatment and the recurrence, and the serum squamous cell carcinoma antigen level at the recurrence. RESULTS: Of the 3137 patients with uterine cervical carcinoma in stages Ia-IVa, 67 (2.1%) experienced recurrence in isolated para-aortic lymph nodes. Stratified by clinical stage, none of the 613 patients with stage Ia experienced recurrence in isolated para-aortic lymph nodes. However, recurrence was experienced by 14 (1.4%) of the 966 patients with stage Ib, 7 (3.5%) of the 199 patients with stage IIa, 14 (2.3%) of the 613 patients with stage IIb, 1 (2.1%) of the 48 patients with stage IIIa, 26 (4.6%) of the 538 patients with stage IIIb, and 5 (5%) of the 100 patients with stage IVa. The mean duration time between the initial treatment and isolated para-aortic recurrence was 20 months (range, 2-49 months). The correlations between duration time and the clinico-pathological factors (clinical stage, histopathology, serum squamous cell carcinoma antigen level, and treatment method) at the initial treatment were investigated. No statistically significant factors have been revealed in the current study. CONCLUSIONS: The frequency of isolated para-aortic lymph node recurrence was 2.1% and increased with increasing clinical stage at the initial treatment (stage IVa: 5%) in the current study.

Adult↗

PubMed2005

Radiation-induced apoptosis of oligodendrocytes in the adult rat optic chiasm.

OBJECTIVES: The present study characterized glial cell injury provoked in adult rat chiasm within 24 hours after a single, high-dose irradiation of 20 Gy. METHODS: All chiasmal glial cells in a section were counted, and the percentage of TUNEL-positive glial cells exhibiting apoptotic morphology was defined as the apoptotic rate. RESULTS: Numbers of apoptotic cells increased significantly (p<0.0001) from 3 to 8 hours after exposure, but returned to baseline levels by 24 hours. Little evidence of apoptosis was observed in non-irradiated chiasms. Similar patterns of increase in apoptotic rate were observed in the genu of the corpus callosum, but the extent was significantly lower (p=0.047) in the optic chiasm, with a maximal rate of 1.9%. Immunohistochemically, apoptotic cells were positive for CNP, a marker for oligodendrocytes. DISCUSSION: These data indicate that chiasmal irradiation induces limited, but significant apoptotic depletion of the oligodendroglial population, and may participate in the development of radiation-induced optic neuropathy.

Analysis of Variance↗

PubMed2002

KF24345, an adenosine uptake inhibitor, suppresses lipopolysaccharide-induced tumor necrosis factor-alpha production and leukopenia via endogenous adenosine in mice.

3-[1-(6,7-Diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazolinedione hydrochloride (KF24345) is a novel potent adenosine uptake inhibitor. KF24345 inhibited [(3)H]adenosine uptake into erythrocytes from human, mouse, rabbit, and hamster with IC(50) values of 59.5, 130.1, 104.2, and 30.9 nM, respectively. In mice, oral administration of KF24345 at 10 mg/kg almost completely inhibited the [(3)H]adenosine uptake into sampled blood cells at least up to 10 h of the administration. In this study, to examine whether the adenosine uptake inhibition exhibits anti-inflammatory effects, we determined the effects of KF24345 on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production and leukopenia in mice. KF24345 (10 mg/kg p.o.) significantly suppressed the elevation of serum TNF-alpha concentration after the LPS injection, and the suppressing effect of KF24345 was abolished by the treatment with 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol, a selective adenosine A(2) receptor antagonist, but not with 8-(noradamantan-3-yl)-1,3-dipropylxanthine, a selective adenosine A(1) receptor antagonist. KF24345 (10 mg/kg p.o.) also inhibited the decrease of leukocytes after the LPS injection, and 8-(p-sulfophenyl)theophylline, a nonselective adenosine receptor antagonist, completely reversed the inhibitory effect of KF24345. These results demonstrate that KF24345 inhibits LPS-induced TNF-alpha production and leukopenia via enhancing the effect of endogenous adenosine. It is thus suggested that the adenosine uptake inhibitor has anti-inflammatory effects in vivo and represents a novel therapeutic approach to the treatment of various inflammatory diseases.

Adenosine↗

PubMed2002

Dose evaluation and effective dose estimation from multi detector CT.

Computed tomography (CT) has evolved remarkably through device improvement and advancement of peripherals, including computers. In 1999, multi detector-row CT (MDCT) appeared and rapid high-speed scanning became possible. However, usefulness of MDCT in actual clinical application cannot be assessed until the exposure doses are assessed appropriately. Since CT examinations need a comparatively high dose, it is necessary to evaluate patient exposure for introduction of MDCT. Patient doses by three types of MDCTs were evaluated for cases of scanning of the chest and abdomen-pelvis. The examination conditions were the same as those in actual clinical examinations. The obtained effective doses were 9.4-28 mSv for the chest examination and 13-28 mSv for the abdomen-pelvis. The average surface doses varied between 16-43 mGy for the chest examination and 20-37 mGy for the abdomen-pelvis. The highest surface dose was 57 mGy for the abdomen-pelvis examination. The exposed doses differed according to scanning method and imaging conditions such as tube current, slice thickness and so on. It seemed that there is room for dose reduction by proper adjustment of scan conditions in MDCT examinations.

Humans↗

PubMedDate not supplied

Results of radiation therapy for superficial esophageal cancer using the standard radiotherapy method recommended by the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

BACKGROUND: Superficial esophageal cancer (SEC) is defined as esophageal cancer limited to the submucosal layers, including mucosal cancer and submucosal cancer, and is squamous cell carcinoma in most patients. In 2000, the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group for SEC published a consensus guideline of standard radiotherapy methods. In this study, the interim treatment outcomes of SEC patients, who had received radiation therapy following the standard radiotherapy methods, were investigated. PATIENTS AND METHODS: From 2000 to 2003, a total of 141 SEC patients were treated in 24 institutions in Japan. RESULTS: The 1-, 2- and 3-year survival rates were 95%, 90% and 90%, respectively, for patients with mucosal cancer and 90%, 81% and 70%, respectively, for patients with submucosal cancer. The overall survival was better in patients who had undergone chemotherapy than in patients who had received radiation therapy alone, though the difference was not statistically significant. The clinical target volume (CTV) did not influence overall survival and intracavitary irradiation did not influence the local control rate in either patients with mucosal or submucosal cancer. Radiation-induced esophageal ulcer was not observed in this series. CONCLUSION: The standard radiotherapy methods are safe and effective for treating SEC. However, the usefulness of chemotherapy and intracavitary irradiation and the optimal setting of the CTV should be clarified by future randomized trials.

Aged↗