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Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins.

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.

Adult↗
PubMed1997

Microdialysis assessment of fibrin glue containing sodium alginate for local delivery of doxorubicin in tumor-bearing rats.

This study was designed to assess a local drug delivery system of an anticancer agent, doxorubicin (DOX), using fibrin glue (Beriplast P) as a drug carrier. In vitro release of DOX from the fibrin glue was examined by a dialysis method in the presence and absence of sodium alginate. The in vitro mean dissolution times of DOX with solution, fibrin glue, and fibrin glue containing sodium alginate were 3.7 h, 8.7 h, and 81 h, respectively, indicating a sustained release of DOX from fibrin glue, especially in the presence of sodium alginate. Fibrin glue containing 6 mg of DOX and 2.5 mg of sodium alginate was applied on the surface of an AH60C tumor at the back of rats. DOX concentrations in the tumor extracellular fluid were monitored by a microdialysis method. Local application of DOX using fibrin glue containing sodium alginate to the tumor resulted in extremely higher concentrations in the tumor extracellular fluid than those in plasma (AUC ratio > 800), indicating an advantage of the site-specific delivery of DOX using fibrin glue with sodium alginate. The tumor volumes were inversely correlated with tumor extracellular fluid-to-plasma AUC ratios (r = 0.882), suggesting the relevance of tumor size in the drug efflux from tumor to blood. In conclusion, the site-specific delivery of DOX using fibrin glue with sodium alginate to the tumor was demonstrated to be advantageous with regard to the extent and duration of drug concentrations in the tumor extracellular fluid, as assessed by a microdialysis technique.

Alginates↗
PubMed1997

Rectal absorption of ozagrel from a suppository containing its commercial tablet in healthy human subjects.

A suppository containing an ozagrel tablet was prepared using Witepsol H-15 as a base, and its rectal absorption was studied in male human volunteers. In comparison, a commercially available ozagrel tablet was administered orally to all the individuals in a cross-over design. After rectal dosing, ozagrel was absorbed rapidly at a Tmax of 0.75 h, and its elimination half-life was longer than after oral dosing. The extent of absorption of ozagrel after both administration routes was similar. However, the bioavailability of the rectal suppository is 92 +/- 37% (mean +/- S.D.; n = 6) relative to the oral tablet. The tablet-containing suppository is easy to prepare, with its content being accurate and reproducible. Thus, the present study suggests that the rectal administration of an ozagrel suppository is a practical and promising alternative to oral administration, especially for patients who cannot take tablets orally. This study demonstrated for the first time the possibility of an ozagrel suppository in human subjects.

Adult↗
PubMed1997

Pharmacokinetics of a Chinese traditional medicine, danshensu (3,4-dihydroxyphenyllactic acid), in rabbits using high-performance liquid chromatography.

An injectable solution of Danshen was prepared and its in vivo disposition was examined in rabbits. The presence of Danshensu, one of the active components of Danshen, in the obtained solution was confirmed by a simple high-performance liquid chromatographic (HPLC) method. The pharmacokinetics of Danshensu in rabbits was evaluated by the HPLC method for plasma Danshensu. The calibration curve for Danshensu was linear (r = 0.998) over the concentration range of 0.25-40.0 micrograms/ml. The intra-assay coefficients of variation (CVs) were 3.8, 3.1, and 3.1% at 1, 10, and 50 micrograms/ml, respectively, and the inter-assay CVs were 5.3, 5.3, and 2.9% at 1, 10, and 50 micrograms/ml, respectively. The analytical recovery of Danshensu in plasma averaged 95.2%. From the plasma concentration profile of Danshensu after its intravenous administration, the t1/2, mean residence time (MRT), Vdss, and Cltot were determined as 32 min, 48 min, 149 ml/kg, and 3.13 ml/min/kg, respectively.

Animals↗
PubMed1997

[Usefulness of 99mTc-tetrofosmin myocardial scintigraphy before and after coronary intervention].

Dipyridamole-loading 99mTc-tetrofosmin myocardial scintigraphy was performed for patients with coronary artery disease who underwent percutaneous transluminal coronary angioplasty (PTCA) in order to examine whether SPECT imaging prior to treatment is useful for the determination of prognosis after coronary intervention. Thirty-six patients including 9 with angina pectoris (AP), 22 with old myocardial infarction (OMI) and 5 OMI with AP were underwent dipyridamole-loading 99mTc-tetrofosmin myocardial SPECT before and after coronary intervention. The length of follow-up was 185 +/- 107 days after PTCA. Improvement of myocardial uptake was observed on myocardial SPECT in all cases with AP. Improvement of the myocardial uptake was observed 50% (4/8) of patients with OMI who had no myocardial viability. It was suggested that the improvement of myocardial uptake after PTCA was due to incomplete fill-in in cases with AP and that the presence of fill-in was important for level of fill-in in patients with AP. The improvement of myocardial uptake in the scar tissue in patients with OMI contributed to the hibernating myocardium. We concluded that correct detection of hibernating myocardium was difficult despite the superior imaging capability of 99mTc-tetrofosmin myocardial SPECT.

Aged↗
PubMed1997

Prediction of wall motion improvement after coronary revascularization in patients with postmyocardial infarction: diagnostic value of dobutamine stress echocardiography and myocardial contrast echocardiography.

The diagnostic value of dobutamine stress echocardiography, myocardial contrast echocardiography and dipyridamole stress thallium-201 single photon emission computed tomography (SPECT) for predicting recovery of wall motion abnormality after revascularization was evaluated in 13 patients with postmyocardial infarction. Seventeen segments showed severe wall motion abnormalities before revascularization. Nine segments which had relatively good Tl uptake on delayed SPECT images despite severely abnormal wall motion were opacified during myocardial contrast echocardiography, and showed improved wall motion after revascularization. In contrast, three segments which had poor Tl uptake and severely abnormal wall motion were not opacified during myocardial contrast echocardiography, and showed no improvement in wall motion during dobutamine stress echocardiography and after revascularization. The following three findings were assumed to be signs of myocardial viability: 1) good Tl uptake on delayed SPECT images; 2) improved wall motion by dobutamine stress echocardiography; and 3) positive opacification of the myocardium by myocardial contrast echocardiography. Myocardial contrast echocardiography had the highest sensitivity (100%) and negative predictive value (100%). Delayed SPECT images had the highest specificity (100%) and positive predictive value (100%). Dobutamine stress echocardiography had a sensitivity of 83.0%, specificity of 80.0%, positive predictive value of 90.9%, and negative predictive value of 66.7%, respectively. Myocardial contrast echocardiography showed the lowest specificity (60.0%). The techniques of dobutamine stress echocardiography and SPECT, though noninvasive, may underestimate wall motion improvement after revascularization. Further examination by myocardial contrast echocardiography is recommended to assess myocardial viability for determining the indications for coronary revascularization in spite of its invasiveness.

Cardiotonic Agents↗
PubMed1996

The accuracy of color Doppler flow imaging for the detection of symptomatic deep venous thrombosis in Chinese patients.

To evaluate the ability of color Doppler flow imaging (CDFI) to detect deep venous thrombosis (DVT), which is difficult to diagnose clinically, 67 limbs of 60 patients who presented with clinical signs strongly indicative of DVT during the period between June 1988 and June 1992, were examined. The iliac, common femoral, and superficial femoral veins were assessed with the patient in the supine position, and the popliteal vein was examined with the patient prone. Gentle but firm compression with the transducer probe was used to test for the presence of DVT. Ascending contrast venograms were also obtained within 24 h after the ultrasound procedure, with venography being used as the standard for comparison with CDFI. DVT was identified in 63 limbs by contrast venography and in 62 limbs by CDFI. The sensitivity and specificity of CDFI were 98.4% and 100%, respectively, while the positive and negative predictive values were 100% and 80%, respectively. The thromboses were classified into three patterns: the filling type, the local type, and mural thrombus, detected in 63%, 27%, and 10%, of the limbs respectively, with the filling type being the most common in this series. The results of our study illustrated that CDFI is highly sensitive and specific for detecting symptomatic DVT and that it should be gradually substituted for venography in such patients.

Adult↗
PubMed1996

Magnetic targeting of thermosensitive magnetoliposomes to mouse livers in an in situ on-line perfusion system.

We recently reported the preparation and in vitro targeting of dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs) [Viroonchatapan et al. Pharm. Res. 12 1176-1183 (1995)]. The current study was designed to determine whether these novel liposomes can be targeted to the mouse liver with the aid of an extracorporeal magnet. An on-line liver perfusion system consisting primarily of a sample injector, permanent magnets, and a fluorescence detector was established for a real-time measurement of targeting efficiency of TMs containing calcein as a fluorescent marker. Normal and reticuloendothelial system (RES)-blocked livers from mice were used for the perfusion experiments. In the RES-blocked livers, percentage holdings of TMs were 73-80% and 26-45% in the presence and absence of magnetic field, respectively, indicating an efficient targeting of TMs with a targeting advantage index (TAI) of 1.6-3.1. On the other hand, TAI in the normal livers was found to be 1.1-1.4 and less than that in the RES-blocked livers, suggesting a role of RES uptake of TMs. The effects of DM concentrations in TM suspensions on the percentage holding of TMs were shown to be minor. Liposome concentration dependence was observed for hepatic uptake of TMs, possibly because of the saturation of phagocytosis by Kupffer cells. The present results suggest that TMs would be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.

Animals↗
PubMed1996

Optimization of the formulation design of chitosan microspheres containing cisplatin.

This study describes an orthogonal experimental design to optimize the formulation of cisplatin (CDDP)-loaded chitosan microspheres (namely, CDDP-DAC-MS) which were produced by an emulsion-chemical cross-linking technique. Seven factors and three levels for each factor that might affect the formulation of microspheres were selected and arranged in an L27(3(13)) orthogonal experimental table. A desirability function (df) calculated according to the trapping efficiency of CDDP, the drug content (%, w/w), and the size distribution of each batch of microspheres was introduced as an index of the microsphere formulation. The overall desirability functions (DF) were produced and treated by a statistic analytical system to optimize the formulation. Moreover, the contour maps were produced to analyze the influence of the seven factors on the size distribution, the drug content, and the drug trapping efficiency. The established optimum procedure was reproducible. Scanning electron micrographs showed that CDDP-DAC-MS were spherical with a coarse surface. The average diameter, drug content, and drug trapping efficiency of CDDP-DAC-MS were 74.8 microns, 20.8% (w/w), and 77.5%, respectively. The in vitro release of cisplatin from chitosan microspheres in saline was retarded compared with that from saline solution; the release of CDDP from chitosan microspheres was suggested to be controlled by the dissolution and diffusion of the drug from the chitosan matrix.

Chitin↗
PubMed1996

Microdialysis assessment of microfibrous collagen containing a P-glycoprotein-mediated transport inhibitor, cyclosporine A, for local delivery of etoposide.

PURPOSE: This study was designed to assess a local drug delivery system of an anticancer agent, etoposide (VP-16), using microfibrous collagen as a drug carrier. For this objective, the microdialysis method was utilized to investigate the local pharmacokinetics of VP-16. METHODS: Microfibrous collagen sheets (CS) containing 20 mg/kg of VP-16 with and without 40 mg/kg of cyclosporine A (CyA) were prepared and applied on the liver surface of rats. VP-16 concentrations in the liver extracellular fluid (ECF) were monitored by a microdialysis method. RESULTS: The local application of CS containing VP-16 resulted in a relatively long maintenance of drug concentrations in the liver ECF with very low concentrations in plasma. The inclusion of CyA in the CS resulted in 2-fold and 3-fold increases of the AUC and MRT values of VP-16 in the liver ECF, respectively. The liver ECF-to-plasma AUC ratios of VP-16 were 32-39 and 0.17 with local CS application and iv administration, respectively, indicating a remarkable advantage of the local drug delivery system. A pharmacokinetic interaction experiment suggested that the observed increase of the liver ECF concentrations of VP-16 with CyA resulted from inhibition of the biliary excretion of VP-16 by CyA. CONCLUSIONS: We found that the local delivery of the CS containing CyA on the liver surface is advantageous in terms of the extent and duration of liver ECF drug concentrations, when CyA was included in the CS. The effect of CyA was probably derived from the inhibition of P-glycoprotein-mediated biliary excretion of VP-16 by CyA. The usefulness of the microdialysis technique for the assessment of the local drug delivery system was also demonstrated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A late phase II study of RP56976 (docetaxel) in patients with advanced or recurrent breast cancer.

A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata was performed to evaluate anti-tumour activity, time to progression and clinical toxicity in patients with advanced or recurrent breast cancer. The patients, between 15 and 80 years old with performance status (PS) of 0-2, received at least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of the 81 patients enrolled, the 72 eligible for the study were given a total of 327 cycles, with a median of four cycles each. Five patients obtained a complete response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4% (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was observed in patients who had received prior chemotherapy involving anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity were not severe and were reversible. One therapy-related death occurred 10 days after the initial dose was given. These findings indicate that docetaxel has potent activity against metastatic breast cancer, and that the dose of 60 mg m-2 is safe.

Adenocarcinoma↗
PubMed1996

Circulating parathyroid hormone-related protein (109-141) in malignancy-associated hypercalcemia.

For differential diagnosis between hypercalcemia-induced bone metastasis and humoral hypercalcemia of malignancy (HHM), serum parathyroid hormone-related protein (PTHrP) concentrations were measured in normal subjects and patients with malignancy-associated hypercalcemia according to the presence or absence of bone metastasis, using a new sensitive PTHrP(109-141) radioimmunoassay system. The serum PTHrP(109-141) levels in all of 14 patients without bone metastasis were significantly higher than those in normal subjects. However, in four patients with hypercalcemia associated with bone metastasis the levels were nearly the same as those in normal subjects. The time course in two hypercalcemic patients with esophageal carcinoma revealed that serum PTHrP(109-141) levels were elevated before hypercalcemia developed and that changes in PTHrP(109-141) and corrected serum calcium levels were significantly correlated. These findings suggest that determination of serum PTHrP(109-141) may be clinically important not only for differential diagnosis of HHM but also as a useful predictive marker of hypercalcemia.

Adolescent↗
PubMed1996

Pharmacokinetic study of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate after targeted delivery to the lung in mice.

This study describes the pharmacokinetic behaviours of taxol after intravenous administration of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline solution to mice. Taxol-IPM-PLGA-MS were prepared using a solvent evaporation technique. The drug content and trapping efficiency of taxol in the microspheres were 5.09% (w/w) and 98%, respectively; the average diameter of the microspheres was 30.1 microns. Scanning electron microscopy showed that Taxol-IPM-PLGA-MS were spherical with a smooth surface. After administration of the drug saline solution (3 mg taxol/kg), taxol disappeared rapidly from plasma within 4-6 h and distributed extensively in various tissues. The tissue levels and AUCfinite of taxol in the lung were obviously higher than those in plasma but relatively lower than those in kidneys, bile, and liver. The biodistribution of taxol after administration of Taxol-IPM-PLGA-MS (3 mg taxol/kg), on the other hand, was altered significantly from the control (taxol solution) group. No taxol was detected in plasma or bile within 3 weeks, and only very low level of taxol was detected in the kidneys or liver within 48 h. However, taxol concentrations in the lung were increased significantly with the microsphere group; the peak concentration of taxol and AUCfinite in the lung was three times and 500 times higher than those with the taxol solution group, respectively. It was also noticed that the taxol levels in the lung were maintained at relatively high levels (> 10 micrograms/ml) for 3 weeks. Thus, the present study demonstrated the effective targeted delivery of taxol to the lung of mice using Taxol-IPM-PLGA-MS.

Animals↗
PubMed1996

Preparation and characterization of poly(lactic-co-glycolic acid) microspheres for targeted delivery of a novel anticancer agent, taxol.

This study describes the preparation and characterization of poly(lactic-co-glycolic acid) microspheres containing a novel anticancer agent, taxol (namely, Taxol-PLGA-MS). A solvent evaporation technique was utilized to prepare Taxol-PLGA-MS. The trapping efficiency of taxol in the microspheres was greater than 90% and reproducible. The in vitro release rate of taxol from the microspheres was very low, and less than 15% of the initial amount of taxol was released in three weeks, irrespective of the drug loading level. When a chemical additive, isopropyl myristate (IPM), was introduced at the level of 30% (w/w), the release of taxol increased significantly; approximately 70% of the initial amount of taxol was released at a nearly constant rate for three weeks. Elevation of the loaded IPM level to 50% (w/w) produced a more rapid release of the drug. Scanning electron microscopy showed that Taxol-PLGA-MS were spherical with a smooth surface. More than half (55-65%) of the microspheres had a diameter of 20-45 microns. Incorporation of IPM had no significant influence on the particle size, surface morphology, or degradation behavior of the microspheres. It was strongly suggested that the release of taxol from the microspheres was dominated mainly by the drug diffusion in the matrix. As evaluated from the particle size, drug content, and in vitro release property, IPM-containing Taxol-PLGA-MS may be suitable for chemoembolization therapy of cancer diseases.

Adsorption↗
PubMed1996

[Peptide hormone].

Clinical studies have confirmed the efficacy of peptide hormone as a routine tumor marker in the diagnosis, monitoring, and assessment of the prognosis of patients with endocrine tumors. However, in a large number of cancer patients, including those with ectopic hormone-producing tumors, the peptide hormone has limited clinical use as a routine tumor marker because of its poor specificity for tumor tissue and its low concentration in the patient sera. A new analysis product, ProGRP, is a specific and reliable serum tumor marker for small cell lung carcinoma (SCLC). It is useful not only in the evaluation of prognosis but also in the detection of SCLC at an early stage. On the other hand, recently, the RET proto-oncogene has been identified as a gene responsible for multiple endocrine neoplasia (MEN) syndromes: MEN 2A and MEN 2B. In the future, serum peptide hormone markers and molecular genetic markers may be useful in the diagnosis of endocrine tumors.

Biomarkers, Tumor↗
PubMed1996

[Two cases of breast cancer detected by 99mTc-tetrofosmin myocardial scintigraphy].

Breast cancer ranks the second position among the cancer of women in Japan. We report two cases of breast cancer detected by 99mTc-tetrofosmin. First case was 51 years old female with breast cancer (invasive papillotubular carcinoma) and dextrocardia. She received 99mTc-tetrofosmin myocardial scintigraphy to evaluate dextrocardia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy showed myocardium at the right side, gall bladder at the left lower side and abnormal uptake on the left chest wall. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed myocardium at the right side and abnormal uptake on the left chest wall. Second case was 78 years old female with breast cancer (intracystic papillary carcinoma) and arrhythmia. 99mTc-tetrofosmin myocardial scintigraphy was performed to evaluate arrhythmia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy shows hot nodule at the lateral side of the myocardium. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed abnormal uptake at the left lateral side on the chest wall. Both cases appeared illed foci as abnormal uptake with 99mTc-tetrofosmin scintigraphy, although histological diagnosis was different. We conclude that 99mTc-tetrofosmin scintigraphy is helpful for evaluating breast cancer.

Aged↗
PubMed1996

[Value of cancer-related oncoprotein expression as prognostic factors in breast-cancer with one to three axillary lymph nodes positive].

The patient group with breast carcinoma with one to three axillary lymph-node metastases (n1-3) shows a poorer prognosis than the node-negative one but a better prognosis than the group with 4 or more lymph node metastases. Univariate analysis shows that loss of bc1-2 expression, nuclear accumulation of p53, overexpression of c-erbB-2, age at diagnosis, menstrual status, tumor size, histologic grade, number of lymph nodes involved, and estrogen receptor were all significantly associated with the survival rates. Multivariate analysis demonstrated that menstrual status, number of involved lymph nodes, bc1-2, and p53 were significant predictors for overall survival, and that histological grade and number of nodes involved were significant predictors for disease-free survival. Combination of those factors would be useful to select highly aggressive n1-3 breast cancer group.

Axilla↗