Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

BACKGROUND: The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored. CLINICALTRIALSGOV IDENTIFIER: NCT01184807.

Prevention of postoperative pulmonary complications through intensive preoperative respiratory rehabilitation in patients with esophageal cancer.

Postoperative pulmonary complications (PPCs) after esophagectomy have been reported to occur in 15.9-30% of patients and lead to increased postoperative morbidity and mortality, prolonged duration of hospital stay, and additional medical costs. The purpose of this retrospective cohort study was to investigate the possible prevention of PPCs by intensive preoperative respiratory rehabilitation in esophageal cancer patients who underwent esophagectomy. The subjects included 100 patients (87 males and 13 females with mean age 66.5 ± 8.6 years) who underwent esophagectomy. They were divided into two groups: 63 patients (53 males and 10 females with mean age 67.4 ± 9.0 years) in the preoperative rehabilitation (PR) group and 37 patients (34 males and 3 females with mean age 65.0 ± 7.8 years) in the non-PR (NPR) group. The PR group received sufficient preoperative respiratory rehabilitation for >7 days, and the NPR group insufficiently received preoperative respiratory rehabilitation or none at all. The results of the logistic regression analysis and multivariate analysis to correct for all considerable confounding factors revealed the rates of PPCs of 6.4% and 24.3% in the PR group and NPR group, respectively. The PR group demonstrated a significantly less incidence rate of PPCs than the NPR group (odds ratio: 0.14, 95% confidential interval: 0.02~0.64). [Correction added after online publication 25 June 2012: confidence interval has been changed from -1.86~ -0.22] This study showed that the intensive preoperative respiratory rehabilitation reduced PPCs in esophageal cancer patients who underwent esophagectomy.

Prediction of 1H Singlet Relaxation via Intermolecular Dipolar Couplings Using the Molecular Dynamics Method.

Dissolution dynamic nuclear polarization has been applied in various fields, including chemistry, biology, and medical science. To expand the scope of these applications, the nuclear singlet state, which is decoherence-free against dipolar relaxation between spin pairs, has been studied experimentally, theoretically, and numerically. The singlet state composed of proton spins is used in several applications, such as enhanced polarization preservation, molecular tagging to probe slow dynamic processes, and detection of ligand-protein complexes. In this study, we predict the lifetimes of the nuclear spin states composed of proton spin pairs using the molecular dynamics method and quantum chemistry simulations. We consider intramolecular dipolar, intermolecular dipolar between solvent and solute, chemical shift anisotropy, and spin-rotation interactions. In particular, the relaxation rate of intermolecular dipolar interactions is calculated using the molecular dynamics method for various solvents. The calculated values and the experimental values are of the same order of magnitude. Our program would provide insight into the molecular design of several NMR applications and would be helpful in predicting the nuclear spin relaxation time of synthetic molecules in advance.

Frequency and characteristics of endometrial carcinoma and atypical hyperplasia detected on routine infertility investigations in young women: a report of six cases.

Infertility patients are known to be at increased risk of endometrial carcinoma (EC) and atypical hyperplasia (AH). However, the incidence and clinical features of EC and AH in these patients remain to be clarified. In this study, we examined the rate at which a routine infertility workup revealed EC/AH and investigated the clinicopathological features of EC/AH detected in this way. Among patients diagnosed with EC or AH at the Jichi Medical University Hospital between the 10-year period from 1997 to 2006, six patients were referred from Tochigi Central Clinic, a specialized infertility facility. We report the clinicopathological features of these patients and calculate the incidence of EC/AH in patients who underwent infertility investigations at Tochigi Central Clinic. All six patients were younger than 40 and had early stage disease (final diagnosis: EC stage IA: 3, EC stage IB: 1, AH: 2). A total of 19 826 patients underwent routine infertility investigations at Tochigi Central Clinic during the same period. The incidence of EC/AH detected from these investigations was 0.03% (6/19 826) and that of EC was 0.02% (4/19 826): 5-10 times higher than the overall incidence in Japanese women of the same age. Routine infertility investigations may provide an opportunity to examine the corpus uteri of young women in whom examination is otherwise limited, contributing to the early detection of EC/AH.

Behavior of endocrine disrupting chemicals in Johkasou improved septic tank in Japan.

The behavior of estrogens (estrone: E1, 17beta-estradiol: E2, estriol: E3 and ethinylestradiol: EE2) and an androgen (testosterone) in the water and sludge from Johkasou in Japan was investigated. The concentrations of E1, E2, E3 and testosterone in water samples from the Johkasou were 33-500, N.D. approximately 150, N.D. approximately 6,700 and 500 ng/L, respectively. In sludge samples, the concentrations of E1, E2, E3, and testostrerone were N.D. approximately 39, N.D. approximately 6.7, N.D. approximately 60 and 0.2-9.0 ng/L, respectively. EE2 was not detected in all samples. The removal rates of E1, E2, E3 and testosterone in Johkasou were 45%-91%, 66%-100%, 90%-100%, and about 90%, respectively.

Reduction in pituitary desensitization and prolongation of gonadotropin release by estrogen during continuous administration of gonadotropin-releasing hormone in women: its antagonism by progesterone.

The present study was designed to elucidate gonadal steroid influences on gonadotropin release and subsequent pituitary desensitization to GnRH. Sixteen women, 10 of whom were normal and 6 of whom had hypogonadism, were infused with GnRH at rates ranging from 0.313-10 micrograms/h via an indwelling iv catheter for 66 h. Blood samples obtained throughout the GnRH infusion were analyzed for LH, FSH, estradiol, and progesterone. A prompt and substantial release of gonadotropin occurred in women with ovarian failure or during the luteal phase in normal women compared with that during the follicular phase of the menstrual cycle. Thereafter, a gradual decrease in gonadotropin secretion occurred due to pituitary desensitization, which was slower in the follicular phase than in other groups. A dose-related increase in integrated LH release occurred during GnRH infusion, but this response tapered off with administration of large doses of GnRH to women with ovarian failure or during the luteal phase. In contrast, it increased linearly up to the maximum dose of GnRH in the follicular phase. These data suggest that 1) basal levels of estrogen suppress the early rapid release of gonadotropin in response to GnRH and reduce subsequent pituitary desensitization, resulting in the prolonged release of LH; 2) estrogen widens the range of dose-related increases in gonadotropin in response to GnRH; and 3) these effects of estrogen are antagonized by progesterone.

Angiotensin II formation by an alternative pathway during exercise in humans.

OBJECTIVE: We postulated a 'kinin-tensin system' in which angiotensin II (Ang II) is cleaved by one or more serine protease independent of renin or angiotensin converting enzyme (ACE). The aim was to determine whether this alternative Ang II-forming pathway by serine proteases participates in the rise in plasma levels of Ang II during exercise in humans. DESIGN AND METHODS: The study consisted of two double-blind crossover experiments. in experiment 1 six healthy volunteers who had been taking either placebo (group P) or the ACE inhibitor captopril (150 mg/day for 3 days; group C) performed a cycle ergometer graded exercise test at four different exercise intensities: stage 1, half of the intensity at the blood lactate threshold (WLT); stage 2, the intensity at WLT; stage 3, the intensity at 4 mmol/l blood lactate; and stage 4, an intensity between stage 3 and maximum intensity. In experiment 2 the same volunteers took captopril (150 mg/day for 3 days) and performed exercise at an intensity corresponding to 90% of the 4 mmol/l blood lactate intensity for 30 min during intravenous drip injection of a serine protease inhibitor, nafamostat [NAF; 0.2 mg/kg per h; NAF(+) group] or saline [NAF(-) group]. RESULTS: In experiment 1 plasma Ang II levels increased from at rest to after exercise in both groups P and C. Although there was a significant treatment effect, captopril did not significantly alter the exercise-induced changes in Ang II level. In experiment 2 the increase in Ang II level after 30 min exercise in the NAF(+) group was significantly lower than in the NAF(-) group. CONCLUSIONS: These results suggest the presence of an alternative Ang II-forming pathway independent of ACE, and that one or more NAF-sensitive serine protease is responsible, at least partly, for generating Ang II during exercise.

Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects.

The concentration of high-density lipoprotein cholesterol (HDL-C) is inversely correlated with the risk of coronary heart disease. The effects of low-intensity aerobic training on serum HDL-C and other lipoprotein concentrations were examined in healthy elderly subjects. The subjects were randomly assigned to two groups matched for sex, age, height, and weight. The training group (n = 20, 10 men and 10 women aged 67 +/- 4 years) participated in a supervised physical exercise regimen using a bicycle ergometer at an intensity of 50% estimated maximal oxygen consumption (VO2max) for 60 minutes two to four times per week for 5 months. In contrast, the control group (n = 20, 10 men and 10 women aged 68 +/- 4 years) did not perform any particular physical training. The training protocol resulted in significant increases in the VO2max (P < .05), HDL-C, HDL2-C, and HDL2-C/HDL3-C ratio (P < .01). The change in HDL2-C (r = .57, P < .01) and HDL2-C/HDL3-C (r = .63, P < .01) was positively associated with an increase in the total exercise duration per week. In addition, the total weekly exercise duration also showed a significant positive relationship with HDL-C (r = .75, P < .01), HDL2-C (r = .81, P < .01), and HDL2-C/HDL3-C (r = .71, P < .01) after the training period. The changes in body weight and the VO2max were not significantly correlated with any lipid parameters. Low-intensity aerobic training may improve the profile of HDL-C and its subfractions in healthy elderly subjects. Also, the total exercise duration may be an important factor for improving HDL-C and HDL2-C in elderly subjects.

Arrest of follicular development in a patient with 17 alpha-hydroxylase deficiency: folliculogenesis in association with a lack of estrogen synthesis in the ovaries.

The degree of follicular development was examined in a patient with 17 alpha-hydroxylase deficiency that accounted for impairment of estrogen and androgen biosynthesis. The ovarian content of P was markedly higher than those of any other steroids requiring 17 alpha-hydroxylation for synthesis. The morphologic analysis of the ovaries demonstrated that normal follicles could not develop to more than 2.2 mm in diameter, and most follicles with diameters of 1.0 mm or more yielded to atresia. It is known that estrogen and FSH act synergistically on the growth of the follicles. Our data suggest that the follicles can develop up to the size of 2.2 mm in diameter at most with the sole stimulation of gonadotropin.

Intracytoplasmic injection with late spermatids: a successful procedure in achieving childbirth for couples in which the male partner suffers from azoospermia due to deficient spermatogenesis.

OBJECTIVE: To investigate the feasibility of using late spermatids in intracytoplasmic sperm injection (ICSI) for patients in which there is a total lack of normal and testicular sperm. DESIGN: Clinical study. SETTING: Private fertility center with adjacent laboratory facilities. PATIENT(S): Thirty-six males diagnosed with azoospermia underwent testicular biopsy and the resulting spermatids from nine patients were used to fertilize oocytes retrieved from their respective wives by ICSI. INTERVENTION(S): Intracytoplasmic spermatid injection of oocytes with late spermatids obtained by testicular biopsy. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and delivery rates. RESULT(S): Three of the cases resulted in pregnancies with childbirth occurring in all three, identical twins in one, and individual singletons in the other two cases. CONCLUSION(S): It is possible to achieve successful levels of pregnancy and childbirth in cases of azoospermia by intracytoplasmic injection of late spermatids.

Blood pressure lowering effect of low intensity aerobic training in elderly hypertensive patients.

PURPOSE: The purpose of this investigation was to determine the effect of 9 months of low intensity aerobic training on blood pressure in elderly hypertensive patients who were receiving antihypertensive medication. METHODS: The training group (N = 13; mean age 75.4 +/- 5.4 yr) agreed to take part in physical training using a treadmill with an exercise intensity at the blood lactate threshold (LT) for 30 min three to six times a week for 9 months. The rest (N = 13; mean age 73.1 +/- 4.2 yr) served as controls. RESULTS: The resting systolic (-15 +/- 8 mm Hg), mean (-11 +/- 6 mm Hg), and diastolic blood pressures (-9 +/- 9 mm Hg) decreased significantly after 3 months of training and the blood pressure of all participants stabilized at a significantly lower level by the end of the study (9 months) in the training group, whereas no significant changes in blood pressure were found in the control group. Both the pretraining systolic and diastolic blood pressure of those recruited patients negatively correlated with those changes after the training (SBP: P < 0.01; DBP: P < 0.05, respectively). After 1 month of detraining in five patients, the blood pressure levels were similar to those in the pretraining state. The LT increased significantly in the training group (P < 0.01). CONCLUSION: In conclusion, an additional antihypertensive effect of mild aerobic training at the LT was confirmed in elderly patients receiving antihypertensive medication. The cessation of such training in five patients, however, resulted in a relatively rapid return to pretraining levels within a month.

[Intraocular penetration of current antibiotics].

We studied the intraocular penetration of 42 antibiotics in white rabbit eyes between 1980 to 1990 in our department. The parenteral route (intravenous, intramuscular): the ratios of maximum aqueous humor to serum level were 5.28-11.6% in penicillins (PCs), 5.95-20.17% in cephems and 13.4-30.27% in aminoglycosides (AGs). The aqueous concentration of antibiotics reached a peak within 1/4-1 hour after injection. Oral administration: the ratios of aqueous to serum level were 8.52-20.6% in PCs, 3.62-20.11% in cephems, 22.8-75.8% in macrolides (MLs) and 6.38-23.6% in quinolones. The aqueous concentration of antibiotics reached a peak within 1-4 hours after oral administration. The ratio of aqueous to serum level was the highest in MLs. The aqueous level reached a peak faster and the ratio of aqueous to serum level was higher by injection than by oral administration.

[Ophthalmic use of clindamycin-2-phosphate (author's transl)].

Bacterial and clinical experiments for ophthalmic use of clindamycin-2-phosphate (CLDM-2-P) were performed and the results were summarized as follows. 1. The distribution of sensitivity for 100 strains of Staphylococcus aureus isolated in 1975 was in the range of less than or equal to 0.19 approximately greater than or equal to 100 mug/ml, and majority of them (96.0%) were in less than or equal to 0.39 mug/ml. 2. The serum concentration by intramuscular injection of 300 mg and 600 mg CLDM-2-P in a single dose respecitvely reached the peak level after 2 hours and decreased gradually until 12 hours in both of them. 3. Ocular penetrations were examined in rabbit eyes. (1) After instillation of 1% CLDM-2-P solution, the aqueous level reached the highest after 1 hour and measurable after 6 hours. (2) After subconjunctival injection of 5 mg/0.5 ml CLDM-2-P, the aqueous level reached the highest after 2 hours and decreased until 6 hours. (3) After intramuscular injection of 100 mg/kg, the aqueous concentration was recognized from 1 to 8 hours, and peak was reached after 1 hour. 1 to 8 hours, and peak was reached after 1 hour. Aqueous-serum ratio in 1 hour was 37.13%. The ocular tissue concentrations at 2 hours showed relatively high levels in both of outer and inner parts of the eye. 4. The intramuscular injection of CLDM-2-P, 300 approximately 1800 mg daily, against suppurative ocular infections revealed excellent effects on cases of external hordeolum, acute chalazion, lid abscess, orbital phlegmone, corneal infiltration, corneal ulcer, and iridocyclitis purulenta. 5. Side effects: Two cases out of 22 cases complained of diarrhoea and bitter taste after injection, and able to be treated continuously by the drug. No abnormal findings in hepatic and renal tests were observed and no servere side effects like allergic reactions were recognized.

[Ophthalmic application of intravenous cephradine (author's transl)].

Basic and clinical experiments were performed on intravenous cephradine (CED) in ophthalmological field. The results are summarized as follows. 1. Serum concentration: After intravenous injection of 1.0 g CED, in a single dose, to a healthy adult, the peak of serum level (34.0 mug/ml) was attained at 15 minutes, then decreased quickly to 2.3 mug/ml by 6 hours. 2. Ocular penetration in rabbit eye: (1) Aqueous humor concentrations: The peak level of aqueous humor (13.45 mug/ml) was obtained at 30 minutes after intravenous injection of 50 mg/kg, in a single dose. Aqueous/Serum ratio was 38.07%. After instillation of 5 mg/ml solution of CED, 5 times every 5 minutes, the aqueous level was recognized 30 minutes and 1 hour, and no detectable 4 hours. After 50 mg/0.5 ml CED subconjunctival injection, in a single dose, the high aqueous levels were observed at 30 minutes and 1 hour, and still detectable 4 hours later. (2) Ocular tissue concentrations: The ocular tissue concentrations at 30 minutes after intravenous injection of 50 mg/kg CED were high in both outer and inner parts of the eye. After 4 hours, the tissue levels remained relatively high concentrations. (3) CLINICAL RESULTS: Intravenous administration of 0.5, 1.0 or 2.0 g CED 1 or 2 times daily revealed excellent or good effects in 8 of 12 cases, such as external hordeolum, internal hordeolum, lid abscess, chronic dacryocystitis, orbital abscess and corneal ulcer. (4) Side effects: Three cases out of 12 complained burning sensation by intravenous injection of CED, but in neither case was it found necessary to withdraw the drugs. No severe side effects such as allergic reactions were observed. No abnormal findings in hepatic and renal function tests were observed.

[Pharmacokinetics of balofloxacin in the intraocular tissues of pigmented rabbits].

We performed the pharmacokinetics of balofloxacin in plasma and intraocular tissues in pigmented rabbits upon its oral administration. The penetrations of balofloxacin into plasma and aqueous humor of the anterior chamber reached their peaks of 6.46 micrograms/ml and 0.70 microgram/ml, respectively, and the ratio of drug concentration in aqueous humor to that of plasma was 0.12 at 1 hour after an oral administration of 20 mg/kg. Concentrations in plasma and aqueous humor of the anterior chamber reached 0.27 microgram/ml and 0.18 microgram/ml, respectively, at The T 1/2 (alpha) and T 1/2 (beta) of the drug in aqueous humor were longer than those in plasma The T 1/2 (alpha) and T 1/2 (beta) of the drug in aqueous humor were longer than those in plasma at a dose of 20 mg/kg. The concentrations in iris and ciliary body were much higher than in any other intraocular tissue in 24 hours after single administration of 20 mg/kg, and those concentrations remained at high levels for a long time.

[Exposure to blood during midwifery procedures--blood contact events to midwives occurred in a delivery room].

Midwives are often exposed to blood during delivery procedures. A study aimed at clarifying actual status of blood contact during midwifery procedures was performed. Observations in a delivery room were conducted to record blood contact events experienced by midwives from the time of episiotomy until 2 hour after expulsion of the placenta. All gloves used by midwives were collected and tested for holes. Blood contact was defined as any contact with blood of a parturition woman as recognized visually by an observer. During a one-month study period data was obtained from a total of 19 midwives (12 midwives and 7 student midwives) who assisted in 8 deliveries. All of the midwives wore gowns with long sleeves, gloves and caps but did not use eye protection or masks. None of the parturient women had Hepatitis B, Hepatitis C or acquired immunodeficiency syndrome. Deliveries caused widespread blood exposure to the midwives throughout the complete course. Protection from most of this exposure was provided by the gowns and gloves. However, direct blood contacts occurred to the fingers, hands or forearms in several midwives. These events were caused by partly because the midwives unintentionally performed procedures without gloves and partly because blood penetrated the gown and soaked to the skin. Direct blood contacts to the foot in two midwives and to the mouth in one also occurred. The overall perforation rate for gloves examined was 4 out of 154 (2.6%). Two gloves were broken during washing sharp instruments contaminated with blood, one was torn when wearing, and the remaining one appeared to have had a hole prior to use.(ABSTRACT TRUNCATED AT 250 WORDS)

[Exposure to blood during midwifery operations--a questionnaire study].

A self-administered questionnaire was mailed to all midwives working in Nara Prefecture to investigate blood exposure events at delivery and to consider protective measures for the exposure. Out of the 203 midwives 193 responded to the questionnaire. The median number of deliveries in which the midwives had assisted within the past one year was 35 after excluding those who had not assisted in deliveries at all. The incidence of needle-stick injuries was estimated to be 86.2 per 100 persons within the past one year. The occurrence in the subgroup who had worked as midwife for less than 5 years was 2-3 times higher than that in those who worked for more than 5 years. Over 90% of the midwives had experiences of direct blood contact events to the skin while assisting in their 10 most recent deliveries. Blood contact events occurred in the finger-hand-arm area in 85% of the midwives, on the legs in 62%, in the face in 20% and in the eyes in 1%. Around 20% of the midwives had unintentionally sucked amniotic fluid when using a tracheal catheter on a newborn. The most common occasion where direct blood contact events occurred was while bathing an infant for removing blood and amniotic fluid. The midwives wore a disposal gown more often when assisting in labors of parturient women infected with blood-born infectious diseases than without the diseases, and similarly for wearing gloves when measuring blood loss and for usage of a mechanical device for sucking amniotic fluid in the tracheae of an infant. Based on the results obtained in this questionnaire study and our previous study about blood contact events observed in a delivery room, protective measures for midwives against exposure to blood at delivery are required and some ideas are presented.

[The effects of low intensity aerobic training on the physiological indexes and the quality of life in middle-aged white collar workers].

The effects of short-term low intensity aerobic training on the physiological indexes and the Quality of Life were examined in 43 middle-aged White Collar Workers. Training was carried out for 205 +/- 117 minutes/week, at least 2-3 times/week for 2 months on a cycle ergometer or walking with intensity level set at the 50% VO2max. Following this training protocol, thirty-six men (exercise group) completed the 2-month training program and 7 men dropped out (the dropout group). In the exercise group, both the VO2max (l/min) and VO2max/wt increased significantly (VO2max (l/min): P < 0.05. VO2max/wt: P < 0.01), whereas the weight, body mass index, %fat, fat (kg) and the waist hip ratio (WHR) decreased significantly (WHR: P < 0.05, others: P < 0.01) after 2 months. In addition, the DBP and serum TC, LDL-c/HDL-c decreased significantly (LDL-c/HDL-c: P < 0.01, others: P < 0.05) whereas the HDL-c increased significantly (P < 0.05). A modified Croog questionnaire was used to assess the subject's Quality of Life. The questionnaire consisted of 59 questions and the overall assessment was based on eight components. Regarding the Quality of Life, physical symptoms, work performance and satisfaction, total Quality of Life all improved significantly (physical symptoms, P < 0.05; others: P < 0.01) and social participation also tended to improve (P < 0.08). There was a significantly negative correlation between the initial Quality of Life and the changes in the Quality of Life (6 of the 8 components). In the all subjects, there was a significantly positive correlation between the changes in physical symptoms and the changes in VO2max/wt (r = 0.36, P < 0.05). In the dropout group, the FBS increased significantly (P < 0.05) but no other variables regarding the Quality of Life significantly changed after 2 months. In conclusion the above results suggest that short-term low intensity aerobic training in the present study can help improve the physiological indexes, VO2max and Quality of Life in middle-aged White Collar Workers and the observed improvement in the Quality of Life was also found to be greater in the subjects with a low Quality of Life than in those with a high Quality of Life.

[Effect of BOF-A2 on experimental and spontaneous metastasis model of mouse colon 26].

We investigated the effects of BOF-A2 on the metastasis of colorectal cancer using artificial (experimental) and spontaneous metastasis of Colon 26 tumor cells. BOF-A2 suppressed pulmonary nodules in the artificial metastasis of Colon 26 tumor cells into the lung, and the T/C (%) was 53.1% at 20 mg/kg or 8.3% at 40 mg/kg. BOF-A2 also suppressed pulmonary nodules in the spontaneous metastasis of Colon 26 tumor cells into the lung, and the T/C (%) was 33.3% at 40 mg/kg in postoperative treatment, 33.3% at 10 mg/kg, or 16.7% at 20 mg/kg in preoperative treatment. These effects were accompanied by the prolongation of survival time at each dose. From these results, BOF-A2 showed antimetastatic activity and survival effect, and may be useful for adjuvant chemotherapy to prevent cancer from metastasis to the lung.

[Exercise therapy].

Accumulating evidence indicates that physically active subject have lower all cause morbidity and mortality than those of sedentary subject. It has been established that low intensity aerobic training improve coronary risk by increasing HDL, HDL2-cholesterol, apolipoprotein-AI and HDL-C/TC, and decreasing triglyceride. Also low intensity training lowers blood pressure and improve insulin resistance. It would be suggested that regular aerobic training may decrease in fibrinogen, platelet aggregation and PAI-1 antigen, and increase in t-PA activity. The low intensity training at 50% VO2max for 60 min/day, 3 times a week can be recommended to exercise therapy in the wide-variety of subjects including coronary heart disease.